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doi:10.3748/wjg.v18.i15.1773
World J Gastroenterol 2012 April 21; 18(15): 1773-1780
ISSN 1007-9327 (print) ISSN 2219-2840 (online)
© 2012 Baishideng. All rights reserved.
BRIEF ARTICLE
Safety and eficacy of Profermin® to induce remission in
ulcerative colitis
Aleksander Krag, Hans Israelsen, Bjørn von Ryberg, Klaus K Andersen, Flemming Bendtsen
Aleksander Krag, Flemming Bendtsen, Gastrounit, Medical
Devision 360, Copenhagen University Hospital Hvidovre, Faculty
of Health Sciences, Copenhagen University, DK-2650 Hvidovre,
Denmark
Hans Israelsen, Bjørn von Ryberg, Nordisk Rebalance A/S, M.
D. Madsensvej 14-16, DK-3450 Allerød, Denmark
Klaus K Andersen, Statistics Section, Informatics and Mathematical Modelling, Technical University of Denmark, DK-2800
Lyngby, Denmark
Author contributions: Israelsen H, von Ryberg B and Andersen
KK conceived the study and developed the overall design; Israelsen H and von Ryberg B performed the study; Andersen KK
performed the statistical analyses and all authors participated in
the interpretation of the overall results; all authors had full access to all data; Krag A drafted the paper and all authors participated in the critical revision for important intellectual content.
Supported by Danish Innovation Law Grant, J.nr. 3414-06-01530,
from the Danish Food Industry Agency under the Ministry of
Food, Agriculture and Fisheries; and Nordisk Rebalance, who
developed and manufactured Profermin®, and partly financed
the study
Correspondence to: Aleksander Krag, MD, PhD, Gastrounit,
Medical Devision 360, Copenhagen University Hospital Hvidovre, Faculty of Health Sciences, Copenhagen University, Kettegaard Alle 30, DK-2650 Hvidovre,
Denmark. aleksanderkrag@hotmail.com
Telephone: +45-3-8623182 Fax: +45-3-8623777
Received: August 15, 2011 Revised: October 23, 2011
Accepted: January 18, 2012
Published online: April 21, 2012
RESULTS: In an intention to treat (ITT) analysis, the
mean reduction in SCCAI score was 56.5%. Of the
39 patients, 24 (62%) reached the primary endpoint,
which was proportion of patients with ≥ 50% reduction in SCCAI. Our secondary endpoint, the proportion of patients in remission deined as SCCAI ≤ 2.5,
was in ITT analysis reached in 18 of the 39 patients
(46%). In a repeated-measure regression analysis,
the estimated mean reduction in score was 5.0 points
(95% CI: 4.1-5.9, P < 0.001) and the estimated mean
time taken to obtain half the reduction in score was
28 d (95% CI: 26-30). There were no serious adverse
®
events (AEs) or withdrawals due to AEs. Profermin
was generally well tolerated.
CONCLUSION: Profermin® is safe and may be effective in inducing remission of active UC.
© 2012 Baishideng. All rights reserved.
Key words: Ulcerative colitis; Diet; Probiotic; Profer®
min ; Inlammatory bowel disease; Dietary management; Medical foods
Peer reviewer: Alan C Moss, MD, FACG, Assistant Professor
of Medicine, Director of Translational Research, Center for
Inflammatory Bowel Disease, Beth Israel Deaconess Medical
Center, Harvard Medical School, Rose 1 / East, 330 Brookline
Ave, Boston, MA 02215, United States
Krag A, Israelsen H, von Ryberg B, Andersen KK, Bendtsen F.
Safety and eficacy of Profermin® to induce remission in ulcerative colitis. World J Gastroenterol 2012; 18(15): 1773-1780
Available from: URL: http://www.wjgnet.com/1007-9327/full/
v18/i15/1773.htm DOI: http://dx.doi.org/10.3748/wjg.v18.
i15.1773
Abstract
AIM: To test the eficacy and safety of Profermin® in
inducing remission in patients with active ulcerative
colitis (UC).
METHODS: The study included 39 patients with mild to
moderate UC deined as a Simple Clinical Colitis Activity Index (SCCAI) > 4 and < 12 (median: 7.5), who were treat®
ed open-label with Profermin twice daily for 24 wk. Daily
SCCAI was reported observer blinded via the Internet.
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INTRODUCTION
Ulcerative colitis (UC) is a chronic relapsing bowel dis-
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Krag A et al . Profermin® in ulcerative colitis
ease characterized by colonic mucosal inflammation.
The goal of treatment in UC is to induce and maintain
remission of the disease. Failure to induce remission
occurs in 20%-30% of patients on current treatments,
leaving colectomy as the only alternative in a proportion of patients[1,2]. Furthermore, many patients ind the
side effects of treatment with corticosteroids and other
drug therapies unacceptable. Accordingly, new treatment
alternatives are being sought. The pathogenesis of UC
has still not been determined in detail; however, a major hypothesis is suggested to be an aggressive immune
response to the intestinal content including, a subset of
nonpathogenic enteric bacteria in genetically predisposed
individuals. Clinical and experimental studies point towards alterations in the relative balance of aggressive
and protective bacterial species in these disorders[3,4].
Interventions to alter the intestinal microlora in order
to decrease proinlammatory stimuli and increase antiinlammatory signaling are under investigation[3,5,6]. Some
studies have suggested an effect of probiotics in the treatment of UC[5,7-9]. The effects of probiotics on the microlora may only be limited and transient because colonization and survival of the probiotics are dificult to achieve.
However, remission from inflammatory bowel diseases
may be induced by food for special medical purposes
(FSMPs), e.g., elemental diets. In this study we investigated
a new dietary product Profermin®, which is intended to
be registered as a FSMP for the dietetic management of
UC. It consists of fermented oats, Lactobacillus plantarum
(L. plantarum) 299v, barley malt, lecithin and water. Our
aim was to investigate the safety and possible eficacy of
Profermin® in patients with mild to moderate UC. We
also assessed the usefulness of a new online daily symptom registration system.
Table 1 Simple Clinical Colitis Activity Index
Symptom
Bowel frequency (d)
1-3
4-6
7-9
>9
Bowel frequency (night)
1-3
4-6
Urgency of defecation
Hurry
Immediately
Incontinence
Blood in stool
Trace
Occasionally frank
Usually frank
General wellbeing
Very well
Slightly below par
Poor
Very poor
Terrible
Extracolonic features
Score
0
1
2
3
1
2
1
2
3
1
2
3
0
1
2
3
4
1 per manifestation
interested and had the relevant disease characteristics to
contact the trial nurse. The patients had to sign a declaration stating when and where they had been diagnosed
with UC and describing the course of their disease including the fulillment of the inclusion criteria. The data
were conirmed by cross checking the patients’ medical
records. A specialist had diagnosed all patients.
Patients were excluded if UC medication was modiied during the study period, however, a dose reduction
of ongoing drugs was accepted. The patients were also
excluded if new medication that may affect UC symptoms was prescribed for other conditions.
MATERIALS AND METHODS
Patients
The study was conducted between 2008 and 2009. Patients were eligible if they were between 18 and 50 years
of age and had an established diagnosis of UC based
on clinical, endoscopic and histological features. Active
disease was assessed by Simple Clinical Colitis Activity
Index (SCCAI) (Table 1) score > 4 and < 12[10]. Patients
who initiated treatment with azathioprine, 6-mercaptopurine, cyclosporin or methotrexate within 8 wk prior
to inclusion or tumor necrosis factor-α inhibitors within
12 wk before inclusion or had changes in UC treatment
within 2 wk before inclusion were ineligible for the
study. Concomitant celiac disease, lactose intolerance
and irritable bowel syndrome were also exclusion criteria.
In addition any malignant or premalignant condition or
recent gastroenteritis and irritable bowel syndrome rendered patients ineligible. Patients were recruited through
advertisement on the website of the local patients’ association, in local newspapers and through Google ads.
The advertisement showed a link to a website that briely
described the trial and encouraged patients who were
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[10]
Outcome measures
Our primary endpoint was to estimate the proportion
of patients with a ≥ 50% reduction in SCCAI. Our
secondary endpoint was to estimate the proportion of
patients in remission deined as SCCAI ≤ 2.5[11].
Study design and assessment of outcome measures
A prospective open-label study design was used to gain
experience with time to response and remission and
compliance for the later design of a comprehensive
controlled study. After a run-in period of 6-14 d, the
patients were followed for 24 wk with daily SCCAI score
assessment. The SCCAI was chosen for the following
reasons. The SCCAI score has been shown to correlate
well with the more complex and invasive scoring systems
and it facilitates daily and observer blinded symptoms
registration[10,11]. Furthermore, colonoscopy may be experienced as painful and therefore compromise the patients’ willingness to participate in a clinical trial. Internet
software was developed by a company specialized in
software development for interactive Internet solutions
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Krag A et al . Profermin® in ulcerative colitis
fermin® is packed in 250-mL cartons under sterile conditions. The product is tested for pH and colony forming
units (CFU) of Enterobacteriaceae, yeasts/moulds and
L. plantarum 299v. The pH must be between 3.6 and 4.2
and the CFU of Enterobacteriaceae, yeasts/moulds must
each be < 100/mL. The CFU of L. plantarum must be >
108/mL.
After 6-14 d of run in, the Profermin® intervention
was initiated by scaling the patient into a daily oral intake
of Profermin®. The initial daily Profermin® dose was
125 mL as the irst meal and 125 mL as the last meal of
the day. After 2 d, the Profermin® dose was increased to
250 mL as the irst meal and 250 mL as the last meal of
the day. However, the protocol was open for periodical
changes of the total dose of Profermin® in the interval
of 25 mL to 500 mL taken once or twice daily, for example, if a patient experienced AEs during the introduction, the low Profermin® dose was prolonged for up to 2
wk. The median dose was 445 mL/d with an interquartile range of 408-500 mL/d. The patients reported their
intake of Profermin® on a daily basis through the trial
website and the mean self-reported adherence therapy
was > 95%.
Patients were recommended to be cautious with
consumption of dairy products and concentrated sugar
products in accordance with routine dietetic recommendations widely used in Danish IBD clinics[6]. Compliance
with this recommendation was not monitored. Patients
continued their usual UC medication and clinical followup with gastroenterologists.
(Franklyweb, Copenhagen, Denmark). The Internet
platform was created according to protocol instructions
and used for individual patient registration of SCCAI
parameters. Regular access to a computer with Internet
access was a criterion for inclusion. Each patient received a username and a password and was instructed to
register the SCCAI parameters daily on the trial website.
Each SCCAI parameter was formulated as a question e.g.
“How many defecations have you experienced during
daytime today? Click on the appropriate answer “1-3”,
“4-6”, “7-9” or ”> 9”. Each SCCAI question needed to
be answered before the patient could continue to the
next question. After registration of the last SCCAI question, the patient was shown an overview of the answers
to every SCCAI question and was asked to conirm or
amend the information. After conirmation, the patient
was shown a graph with the daily SCCAI scores from
the irst day of the run-in period up to the present date.
The patients could communicate on the trial website
with the nurse who checked the status of each patient at
least twice a week and could send reminders if patients
failed to register the daily symptoms. The symptoms
were registered on a daily basis. When a patient failed to
register a day’s symptoms, the patient was reminded by
the nurse about the lacking registration. The registration
rate (registered days out of total number of days) was >
95%. The data were transferred from the patients via the
Internet in encrypted form (Secure Sockets Layer) and
stored on a secure server. The data were instantly copied
- in raw and unprocessed form - to a similar server at
the Technical University of Denmark, Department of
Informatics and Mathematical Modelling, in order to secure the authenticity of the data and to analyze the data
statistically.
Occasionally some patients did not have access to
a computer with an Internet connection. In such cases,
these patients received paper SCCAI questionnaires to
be completed for each day of the relevant period. When
access to the Internet was again established, the patients
transferred the SCCAI parameters noted on the questionnaires to the website. During the screening process,
30 of the included patients (77%) had a face-to-face
meeting with the trial nurse. There were no other faceto-face contacts with the patients. All other communication was electronic (phone or e-mail). The patients were
instructed to report adverse events (AEs) via the trial
website. Safety of Profermin® was assessed by analyzing
the AE reports.
Ethics, approvals and patient consent
The trial was approved by the Danish Data Protection
Agency (2008-41-2961) and has been cleared with The
Ethical Committees of the Copenhagen Region and
registered (H-B-2008-FSP-20). As Profermin ® is an
FSMP and not a medicinal product, no authorization by
the Danish Medicines Agency was required. All patients
gave written informed consent according to the Helsinki
declaration. The study was registered on www.clinicaltrials.gov (NCT01245465).
Statistical analysis
In all analyses, we applied the principle of intention-totreat (ITT). Data for patients who dropped out or who
were excluded during the study period were included in
the analysis by using the principle of last value carried
forward. Unadjusted estimates for the primary and secondary endpoints were presented as total numbers and
percentages. To gain further insight into the longitudinal
effect of Profermin® on the possible decline in SCCAI
over time adjusted for the starting value, we applied the
following non-linear regression model:
Scoreij = b 0 + b 1 × 2-Dayi/q
Where the dependent variable Scoreij was the score for
person j on Day i. Time was denoted by the independent
variable Dayi. In the model, the parameters to be estimated had the following interpretation: b 0 was the ultimate
Description of the intervention
Profermin® is manufactured as follows. Oat gruel is produced by mixing oats, water and a small amount of barley
malt. The mixing process lasts for 1 h at 88 ℃. The gruel
is then cooled to 38 ℃, and a L. plantarum 299v starter
culture is added. The mixture is kept at 38 ℃ for 15 h
with constant gentle stirring. The resulting oat-fermented
gruel is cooled to about 8 ℃. Lecithin is then added
while the mixture is gently stirred and the resulting Pro-
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Patient relection on advertisements in
newspapers, the patients’ association
website and Google Ads.
N = 401
Telephone call
N = 360
Patient excluded
Inclusion criteria not met
Nurse asking for patient’s data.
Analysis in relation to inclusion and
exclusion criteria
N = 41
Criteria met
A run-in period of 6-14 d begins
The patient enters the SCCAI symptoms
daily on the website
N=2
Patient excluded
A-SCCAI not approved
Average-SCCAI (A-SCCAI) for run-in is
calculated. Must be
4 < A-SCCAI < 12
Average-SCCAI approved
Patient excluded
N=0
Consent and relevant
data and signatures not
provided
Consent and relevant data and
signatures provided
N = 4 excluded due to protocol
violation on Days 10, 58, 110,
117. Three were prescribed
antibiotics and 1 corticosteroids.
N = 8 drop-outs on
Days 9, 66, 81, 107,
111, 136, 147, 148
Personal or telephone meeting between
patient and nurse. Checking data and
obtaining patient’s consent. Profermin
is provided
N=4
Excluded
The 24-wk treatment course begins
N=8
End of treatment
N = 39
On a daily basis:
Intake of Profermin
Entering symptoms on the website
N = 27
Drop-outs
Figure 1 Patient low diagram. SCCAI: Simple Clinical Colitis Activity Index.
score (or asymptote), b 1 was the total reduction in score
and q was the time taken to obtain half the reduction in
score. Besides giving the parameters a marginal interpretation, it was of interest to describe the between-patient
variation. Thus, we applied a nonlinear mixed-effects
model, assuming that all three parameters in question
followed a Gaussian distribution, i.e., each parameter
was person-speciic:
Scoreij = b 0,j + b 1,j × 2-Dayi/qj
Here, we assumed that b 0,j = N(b 0,sb 0), b 1,j = N(b 1,sb 1)
and q j = N(q ,sq ). The mixed-effect model led to the following interpretation: the estimated parameter sb 0 was the
between-person SD regarding the asymptote. Similarly, sb 1
was the between-person SD related to the total reduction
in score, and sq was the between-person SD related to the
time taken to obtain half the reduction in score.
Before making inference, we examined both standardized residuals and estimated random effects for
marginal normality by applying normal probability plots.
In all statistical analysis, the software R and the package
nlme were used. All tests were done as likelihood ratio
tests with a signiicance level of 5%.
inclusion criteria were not met (Figure 1). Reasons for
exclusions were primarily SCCAI < 5 or recent change
in oral corticosteroid treatment. During the run-in period, two additional patients were excluded because the
SCCAI criteria were not met. The study comprised 39
patients who were available for ITT analysis: four were
excluded and eight dropped out during the 24-wk treatment period (Figure 2 and Table 2).
Baseline characteristics and use of concomitant medications are shown in Tables 3 and 4.
Safety and tolerability
No major AEs were reported and there were no dropouts due to AEs. An increased number of bowel movements were reported by 11 patients (28%), bloating by
four (10%) and an increased number of bowel movements and bloating by three (8%). All AEs were selflimiting or managed by dose adjustments. For example,
if a patient experienced a presumable AE during the
introduction of Profermin®, the period with the low
Profermin® dose was prolonged for up to 2 wk. None
of the eight dropout or four excluded patients left the
trial due to deterioration in UC symptoms.
RESULTS
Clinical response and remission
Of the 39 patients, 27 completed the entire study. For
those completing the study, the mean follow-up was
The advertisements attracted 401 respondents, of whom
360 were excluded before the run-in period because the
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Krag A et al . Profermin® in ulcerative colitis
Table 2 Description of four excluded patients and eight
dropouts
Day
SCCAI
Reason for
run in discontinuation
Patient
Excluded patients
10
8.9
45
8.0
100
8.2
116
11
Drop-outs
9
8.9
54
4.6
73
5.9
100
5.6
102
9.0
127
6.6
140
6.7
141
8.3
0
50
100
Days since start
150
Reduction Increase
1
1
1
2
6.6
4.1
4.1
3.6
2.3
3.9
4.1
7.4
3
3
3
3
3
3
3
3
6.7
5.1
7.3
8.4
6.7
5.6
5.3
6.3
2.2
0.5
1.4
2.8
2.3
1.0
1.4
2.0
Reasons for discontinuation in the study. 1: Excluded because of new
medication prescribed for unrelated diseases; 2: Excluded because of new
medication prescribed for colitis; 3: Dropouts main reason: Not satisied
with effect of treatment. SCCAI: Simple Clinical Colitis Activity Index.
200
Figure 2 Point indicates that patient has dropped out.
Table 3 Demographic and baseline clinical characteristics of
patients
176 d (range: 174-179 d). For those not completing the
study, the mean follow-up was 94 d (range: 9-141 d). An
ITT analysis showed that the mean reduction in SCCAI
score was 56.5%. For the primary endpoint, ITT analysis
showed that 24 of the 39 patients (62%) achieved a ≥
50% reduction in SCCAI score (Figure 3A). In per protocol (PP) analysis, 85% reached the primary endpoint. In
ITT analysis, four patients (10%) experienced deterioration in SCCAI but 13 (33%) experienced > 75% improvement in SCCAI during the study (Figure 3B). Of the 39
patients, 18 reached the secondary endpoint and obtained
remission defined as SCCAI score ≤ 2.5, with an ITT
success rate of 46% (Figure 3C). In PP analysis, 67%
reached the secondary endpoint remission. Applying only
the four defecation scores in the SCCAI (Table 1), four
patients (10%) had deterioration and 17 (44%) had > 75%
improvement in defecations scores (Figure 3D).
When applying the nonlinear model for the ITT decline in SCCAI over time, the estimated ultimate score
(or asymptote) was 2.8 points (95% CI: 92.0-3.6), the estimated mean reduction in score was 5.0 points (95% CI:
4.1-5.9, P < 0.0001) and the estimated mean time taken
to obtain half of the reduction in score was 28 d (95%
CI: 26-30) (Figure 4).
Profermin, n = 39
Characteristic
Sex, male:female
Age, yr, median and range
Mean duration of disease, yr, median and range
Disease location, n (%)
Proctitis
Left-sided colitis/procto-sigmoiditis
Pancolitis
Extraintestinal manifestations, n (%)
Initial CRP, mg/L, median and range
Initial albumin, g/L, median and range
15/24
35 (19-50)
7 (1-21)
17 (44)
11 (28)
11 (28)
17 (43)
15 (< 1-156)
41 (23-47)
CRP: C-reactive protein.
Table 4 Concomitant medications
n (%)
Mesalamine oral
Alone
Combined with immunosuppressants
Mesalamine enema or suppository
Azathioprine or 6-mercaptopurine
Corticosteroids oral
Corticosteroids enema
Antibiotics
TNF-α inhibitors
None
Descriptions of exclusions and dropouts
Protocol violations accounted for the exclusion of four
patients (10%) - days 10, 45, 100 and 116 (Table 4); three
were prescribed antibiotics for pneumonia, salmonella
infection and gastroenteritis, respectively, and one was
prescribed corticosteroids for UC. Among those excluded, the mean SCCAI on inclusion was 9.0 (range:
8.0-11) and at exclusion 4.6 (range: 3.6-6.6). There were
eight dropouts (20%) (Table 2). Among these, the mean
SCCAI at inclusion was 7.0 (range: 4.6-9.0) and at drop-
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SCCAI
dropout
21 (54)
8 (21)
6 (15)
3 (8)
0 (0)
1 (3)
0 (0)
3 (8)
3 (8)
TNF-α: Tumor necrosis factor alpha.
out 6.4 (range: 5.1-8.4). Among the dropouts, three experienced an increase in SCCAI (mean: 1.6) while in the
study and ive experienced a decrease (mean: 1.8). The
three patients with an increase in their SCCAI score represented treatment failures.
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A
≥ 50% improvement
B
14
Improvement
12
< 50% improvement
Aggravation
10
8
6
4
2
Ag
gr
Ag
>
75
gr
%
50
%
Ag
-7
gr
5%
26
%
-4
Ag
9%
gr
1%
-2
5%
St
at
us
Im
qu
pr
o
1%
Im
2
pr
5%
26
%
Im
-4
pr
9%
50
%
Im 75%
pr
>
75
%
0
Improvement
%
75
5%
pr
Im
Im
pr
>
-7
9%
50
%
-4
5%
-2
Im
pr
26
1%
pr
Im
%
qu
o
5%
us
at
St
1%
gr
gr
Ag
-2
-4
5%
-7
75
gr
50
%
>
gr
Ag
Ag
9%
Aggravation
%
SCCAI > 2.5
18
16
14
12
10
8
6
4
2
0
Ag
D
%
Remission ≤ 2.5
26
C
Figure 3 Intention to treat analysis of the primary (A, B) and secondary (C, D) endpoint. A, B: Proportion of patients with ≥ 50% reduction in Simple Clinical
Colitis Activity Index (SCCAI) at week 24 and the relative development in SCCAI score; A: The primary endpoint was in intention to treat (ITT) analysis reached by 24
in 39 patients (62%); B: Illustrates the relative development in SCCAI in the last week of observation compared to the run-in week; C, D: Remission at week 24 and
the relative development in the 4 defecation scores; C: The secondary endpoint was in ITT analysis reached by 18 in 39 patients (46%); D: Illustrates the relative development in the 4 defecation scores in the SCCAI (Table 1) in the last week of observation compared to the run-in week.
Score = b0 + b12
(-Days/q)
17
for clinical improvement and remission in UC found a
relevant clinical improvement to be a decrease of 1.5 SCCAI points and the best cut-off to establish remission as
an SCCAI of 2.5[11]. In ITT analysis, the average reduction was > 1.5 SCCAI points 12 d after the intervention
was initiated. After 32 d, the average reduction increased
to > 3 SCCAI points and after 84 d to > 4.5 (Figure 4).
In a repeated measure regression analysis, the mean reduction in SCCAI after 24 wk of Profermin® treatment,
adjusted for baseline value, was 5.0 and the estimated
ultimate score was calculated to be 2.8 (Figure 4), suggesting a clinically relevant and signiicant effect. A metaanalysis of response rates in the placebo arms of UC trials estimated the placebo rates of remission and response
to be 13% (95% CI: 9-18) and 28% (95% CI: 23-33),
respectively[12]. The ITT remission and response rates in
our study were 33 and 34 percentage points above these
standard placebo rates, supporting a possible clinical effect of Profermin® when compared with standard placebo rates of response and remission. The safety proile of
Profermin® appears favorable with no major AEs and no
withdrawals due to AEs. Mild AEs were observed mainly
in the initial days of treatment and ceased within a few
days or after dose adjustments. Safety and tolerability of
Profermin® are comparable to those of probiotics[7-9].
Profermin® is a complex product and the mode of
action is probably complex as well. However, dietary
management with Profermin® uses a novel approach and
Observed mean
Fitted mean
Score
10
8
6
4
2
0
0
50
100
Days since start
150
180
Figure 4 Development in Simple Clinical Colitis Activity Index score.
DISCUSSION
In ITT analysis, 62% of the patients reached the primary
endpoint, defined as ≥ 50% reduction in SCCAI, and
46% reached the secondary endpoint of remission, deined as an SCCAI score ≤ 2.5. A study on endpoints
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ment in UC is to induce and maintain remission of the disease, however, failure
to induce remission occurs in 20%-30% of patients on current treatments. Accordingly, new treatment alternatives and additives are being sought. Dietetic
interventions may improve symptoms in UC.
cannot be categorized as a probiotic, prebiotic or symbiotic product[13]. The dietary effect may be related to the
fermented oats components such as the relatively large
amounts of secondary metabolites from the fermentation process and the composition of oats per se. The
short chain fatty acids of secondary metabolites have
been shown to serve as a major source of energy for
colonocytes, and b-glucans have been described as biological response modiiers[14,15]. L. plantarum is a common
species in the human gastrointestinal microbiota[16-18].
L. plantarum 299v survives passage through the gastrointestinal tract and has been isolated from feces and rectal
and jejunal biopsies 11 d after 10 d administration to
healthy volunteers, indicating at least transient colonization of the gut mucosa[19-21]. It has been shown that oat
gruel fermented with L. plantarum 299v increases iron
absorption by 50%, suggesting an important dietary effect for UC[22]. In addition, the phosphatidylcholine (PC)
in lecithin may serve as an important food component
because the content of PC in the colonic mucus of patients with UC is signiicantly lower compared with the
content in healthy controls[23]. Lastly, the daily intake of
relatively large quantities of fermented oats may change
the intestinal contents and environment and thereby establish an altered platform for microbial activity.
In this study, we introduced a new online self-reporting Internet-based system for assessing daily activity
in UC and for monitoring response to treatment. The
system allows electronic monitoring of data and enables
daily reporting with minimal interruption to the patient’
s daily life. The risk of patients being inluenced in their
self-assessment by health personnel is limited. Independent monitoring and statistical analyses can be achieved
easily. In Denmark, where most people have Internet access, this system is a very useful research tool in a population of UC patients.
Our study had some limitations: (1) it was an uncontrolled study and the results need to be conirmed
in a randomized trial; and (2) patients were informed
to consider their consumption of dairy products and
concentrated sugar products, in particular fresh milk and
confectionary. This may have had an effect on UC or
may have reinforced the effect of Profermin®.
The present study demonstrates that Profermin® is
safe and may be effective in inducing remission of active
UC. Randomized controlled studies are planned to explore further the clinical eficacy of Profermin®.
Research frontiers
Clinical and experimental studies point towards alterations in the relative balance of aggressive and protective bacterial species in UC. Interventions to alter
the intestinal microlora in order to decrease disease activity are under investigation and prebiotics, probiotics and symbiotics have been investigated in UC
but the reported eficacies have varied.
Innovations and breakthroughs
This is believed to be the first study to assess Profermin® in UC. The study
was an open label study that investigated safety and eficacy of Profermin® in
patients with moderate active UC. Profermin® is a new developed product for
the dietary management of UC. It is a fermented oat gruel with Lactobacillus
plantarum 299v, barley malt, lecithin and water.
Applications
Profermin® is safe and well tolerated and may be effective in reducing symptoms and inducing remission in UC. Larger randomized trials should be performed to investigate further the eficacy of Profermin® in UC.
Terminology
Simple Clinical Colitis Activity Index (SCCAI) assessed active disease. SCCAI
is a clinical scoring system for UC, based on bowel frequency day and night,
urgency, fecal blood, general well being and extracolonic manifestations.
Peer review
The authors have reported a study on the safety of Profermin®, a combination
of fermented oats, probiotics and lecithin, in patients with mild to moderate UC.
This is primarily an open-label safety study in patients. The agent was welltolerated and may be eficacious.
REFERENCES
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ACKNOWLEDGMENTS
We thank Jørgen Villumsen for invaluable practical and
technical assistance. We also thank Peter Møller and
Carsten Toftager Larsen for important advice during the
study.
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COMMENTS
COMMENTS
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Background
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S- Editor Shi ZF
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L- Editor Kerr C
E- Editor Li JY
April 21, 2012|Volume 18|Issue 15|