Ulcerative ColitisPhase 2ACRENCT04000139
Anthocyanin Rich Extract (ACRE) in Patients With Ulcerative Colitis
A Phase 2 study testing Standardized anthocyanin-rich extract in people with Ulcerative Colitis, run by University of Zurich at 6 sites in Switzerland.
Trial summary
This study evaluates the efficacy and safety of a bilberry derived anthocyanin-rich extract in patients with ulcerative colitis. Two thirds of participants will receive the anthocyanin-rich extract, while one third will receive placebo, for 8 weeks of treatment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Ulcerative Colitis
- What is being tested?
- Standardized anthocyanin-rich extract
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 48 participants
- Where
- 6 sitesSwitzerland
- Study dates
- 1 Apr 2019to 11 Mar 2021
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female ≥ 18 years of age
- Established diagnosis of UC, with minimum time from diagnosis of ≥3 months
- Moderately at least left sided UC (disease should extend 15 cm or more above the anal verge). Disease severity determined by a Modified Mayo score of 6 to 12 with an endoscopic sub score ≥2 assessed by central reading of endoscopy performed at screening visit and no other individual sub score <1 (see 9.8.2 for more detailed information)
- Current oral or rectal 5-ASA/SP use or a history of oral or rectal 5-ASA/SP use
- Current steroids use or history of steroids dependency, refractory, or intolerance, including no steroids treatment due to earlier side-effects (only one of the steroids criteria have to be fulfilled, see definition in European Crohn´s and Colitis organization (ECCO) guidelines)
- One of the following points must be fulfilled:
Show all 17Show fewer
- Active disease despite induction therapy with 5-ASA agents where adequate therapy is considered with an oral 5-ASA (mesalamine 2- 4.8 g/day, sulfasalazine 4-6 g/day) administered for at least 2 weeks. Topical treatment with 5-ASA may have been attempted but this is not a prerequisite for inclusion in the study OR
- Intolerance to oral 5-ASAs or azathioprine OR
- Active disease despite a thiopurine (adequately dosed according to treatment guidelines, such as 2-3 mg/kg for azathioprine) or methotrexate administered for at least 12 weeks.
- Allowed to receive a therapeutic dose of following UC drugs during the study:
- Oral steroids therapy (≤30 mg prednisone or equivalent/daily) providing that the dose has been stable for 2 weeks prior Baseline
- Oral or rectal MMX Budesonide therapy (9mg/daily) initiated and a stable dose at least 2 months before Baseline
- Oral or rectal 5-ASA/SP compounds, providing that the dose has been stable for 2 months prior to Baseline and initiated at least 8 weeks before screening.
- AZA/6-MP providing that the dose has been stable for 8 weeks prior to Baseline and been initiated at least 2 months before screening
- TNF inhibitors (Infliximab, Adalimumab or Golimumab) are allowed, providing that the dose is stable for at least 2 months prior to baseline and during the study treatment period
- Vedolizumab and Tofacitinib is allowed providing that the dose is stable for at least 2 months prior to baseline and during the study treatment period
- Ability to understand the treatment, willingness to comply with all study requirements and ability to provide informed consent
Who cannot join
- Subjects fulfilling any of the following criteria are not eligible for inclusion in this study:
- Suspicion of differential diagnosis such as; Crohn's enterocolitis, ischaemic colitis, radiation colitis, indeterminate colitis, infectious colitis, diverticular disease, associated colitis, microscopic colitis, massive pseudopolyposis or non-passable stenosis
- Acute fulminant UC and/or signs of systemic toxicity
- UC limited to the rectum (disease which extends <15 cm above the anal verge)
- History of malignancy, except for:
- Treated (cured) basal cell or squamous cell in situ carcinoma
Show all 33Show fewer
- Treated (cured) cervical intraepithelial neoplasia or
- carcinoma in situ of the cervix with no evidence of recurrence within the previous 5 years prior to the screening visit
- History or presence of any clinically significant disorder that, in opinion of the investigator, could impact on patient's possibility to adhere to the protocol and protocol procedures or would confound the study result or compromise patient safety
- Long term treatment with antibiotics or non-steroidal anti-inflammatory drugs (NSAIDs) within two weeks prior to screening (one short treatment regime for antibiotics and occasional use of NSAIDS are allowed)
- Serious active infection
- Gastrointestinal infections including positive Clostridium difficile stool assay
- Currently receiving parenteral nutrition or blood transfusions
- Females who are lactating or have a positive serum pregnancy test during the screening period
- Concurrent participation in another clinical study with investigational therapy or previous use of investigational therapy within 5 half-lives and within at least 30 days after last treatment of the experimental product prior to enrolment
- Subjects who have been treated with
- A dose of ≥ 1 mg per kg body weight prednisone or ≥30mg/d in the last 4 weeks prior to randomization.
- Ongoing treatment with cyclosporine or tacrolimus. Eligible subjects must have stopped cyclosporine and/or tacrolimus at least 4 weeks and antibiotics at least 1 week prior to randomization.
- known history of alcohol abuse, chronic liver or biliary disease
- Repeated and confirmed laboratory findings showing:
- total bilirubin greater than 2 x upper limit of the normal range (ULN) unless in context of Gilbert's syndrome
- alkaline phosphatase (AP) greater than 2 x ULN
- ALT (SGPT) greater than 2 x ULN
- serum creatinine greater than 2 X ULN
- total white blood cell count (WBC) outside the range of 3,000 - 15,000 /μL. Subjects with mild leukocytosis (WBC not higher than 15,000 /μL) may be eligible, especially if the elevated WBC, according to the Investigator, is attributable to corticosteroid therapy and other causes such as hematological or infectious diseases can be excluded.
- platelet count <100,000/μL
- Hemoglobin less 8 g/dL and/or other signs of severe anemia.
- History or presence of a significant renal disease.
- Significant illness within the two weeks prior to dosing or any active systemic infection or medical condition that may require treatment or therapeutic intervention during the study.
- Current history of active systemic bacterial, viral or fungal infections
- Presence or history of underlying metabolic, endocrine, hematologic, pulmonary, cardiac, blood, renal, hepatic, infectious, psychiatric or any medically unstable condition, as assessed by the primary treating physician which, in the opinion of the investigator, would place the subject at unacceptable risk for participation in the study.
- Known allergies to bilberries or any other AC containing fruits
- Planned diet change, any severe or new dietary restrictions
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
Switzerland6 sites
Universitätsspital Basel
Basel, 4031
Inselspital Bern
Bern, 3010
Gastroenterologische Praxis Balsiger, Seibold & Partner
Bern, 3012
Centre Hospitalier Universitaire Vaudois
Lausanne, 1011
Kantonsspital St. Gallen
Sankt Gallen, 9007
Universitätsspital Zürich
Zurich, 8091
About this study
Official title: A Multi-center, Multi-national, Randomized, Double-blind, Placebo Controlled, Parallel Group, Phase IIa Study to Evaluate the Efficacy, Safety and Tolerability of an Anthocyanin-rich Extract (ACRE) in Patients With Ulcerative Colitis
This study evaluates the efficacy and safety of a bilberry derived anthocyanin-rich extract in patients with ulcerative colitis. Two thirds of participants will receive the anthocyanin-rich extract, while one third will receive placebo, for 8 weeks of treatment.
Read the detailed description
For anthocyanins (ACs), a wide range of protective biological effects have been described, such as anti-oxidative, anti-carcinogenic, anti-microbial and anti-inflammatory activities. Various research groups could identify a beneficial effect of ACs in IBD and intestinal inflammation.
A total of 112 subjects will be randomized. Subjects will be screened for eligibility between 0 and 28 days prior to baseline visit. At the baseline visit, subjects with moderate to severe ulcerative colitis (Mayo score ≥6) and fulfilling all inclusion/exclusion criteria will be randomized into two treatment arms (ACRE or placebo). Total duration of drug product administration will be 8 weeks (56 days) followed by a follow-up phase of 30 days.
- Conditions
- Ulcerative Colitis
- Being tested
- Standardized anthocyanin-rich extract, Placebo
- Keywords
- bilberry, anthocyanin, anthocyanin-rich extract, ulcerative colitis
- Medical subject headings
- Colitis, Ulcerative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Standardized anthocyanin-rich extractDrug
3g of anthocyanin-rich extract taken daily as: 3 doses of 2x 500mg. Treatment duration 56 days (8 weeks).
PlaceboDrug
3g of placebo taken daily as: 3 doses of 2x 500mg. Treatment duration 56 days (8 weeks).
| Study group | Role | What they receive |
|---|---|---|
| Standardized anthocyanin rich extract | Active comparator | 3 doses of 2x 500mg in capsules daily Receives: Drug: Standardized anthocyanin-rich extract |
| Placebo | Placebo comparator | 3 doses of 2x 500mg in capsules daily Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical response at week 8
Proportion of patients with clinical response at week 8 where clinical response is defined as the reduction of total mayo score ≥ 3 points
Measured: 8 weeks
Secondary outcomes (13)
Clinical remission at week 8
Proportion of patients with symptomatic clinical remission at week 8, where clinical remission is defined as total mayo score ≤ 2, with no individual sub-score > 1
Measured: 8 weeks
Rectal bleeding
Proportion fo patients with absence of rectal bleeding at week 8, defined by the mayo subscore rectal bleeding of 0
Measured: 8 weeks
Stool frequency
Proportion of patients with normal or enhanced stool frequency at Week 8, defined by the Mayo sub score stool frequency of 0 or 1 (with at least one point decrease from Baseline, Week 0)
Measured: 8 weeks
Endoscopic remission
Proportion of patients with endoscopic remission at Week 8, defined by the Modified Mayo endoscopic sub score of 0 or 1 (excluding friability)
Measured: 8 weeks
Histological remission
Proportion of patients with histological remission at Week 8, defined by the Geboes Index of grade 0 or 1
Measured: 8 weeks
Symptomatic remission
Proportion of patients with symptomatic remission at Week 4, defined by the Mayo sub scores, i) rectal bleeding of 0, ii) stool frequency of 0 or 1 (with at least one point decrease from Baseline, Week 0), (patient reported outcome)
Measured: 4 weeks
Rectal bleeding week 4
Proportion of patients with absence of rectal bleeding at Week 4, defined by the Mayo sub score rectal bleeding of 0
Measured: 4 weeks
Stool frequency week 4
Proportion of patients with normal or enhanced stool frequency at Week 4, defined by the Mayo sub score stool frequency of 0 or 1 (with at least one point decrease from Baseline, Week 0)
Measured: 4 weeks
Durable symptomatic remission
Proportion of patients with durable symptomatic remission, defined by the Mayo sub scores, i) rectal bleeding of 0, ii) stool frequency of 0 or 1 (with at least one point decrease from Baseline, Week 0) [PRO2] at both Week 8 and Week 12
Measured: 8 weeks / 12 weeks
Clinical response
Proportion of patients with clinical response at Week 8, defined as clinical remission or a three point and ≥30 % decrease from Baseline, Week 0 in the sum of the Modified Mayo score, i) rectal bleeding, ii) stool frequency and iii) endoscopy score (excluding friability), iiii) physicians global assessment (PGA)
Measured: 8 weeks
Fecal calprotectin
Mean change in fecal calprotectin at Week 1, 2, 4, and 8 compared to Baseline, Week 0.
Measured: 8 weeks
Steroid dosage
Mean change in steroid dosage for patients in remission at Week 8 to Week 12
Measured: 4 weeks (follow-up phase)
SIBDQ
Mean change in each of the short inflammatory bowel disease questionnaire (SIBDQ) sub domains at Week 8 compared to Baseline, Week 0 SIBDQ data will consist of 10 individual items, scores for the 4 dimensions (bowel function, emotional status, systemic symptoms and social function) and a total score. All data will be listed and data for the 4 dimensions and total score summarized by time post-dose for each dose. Week 8 changes from baseline for the 4 dimensions and total score will be plotted and summarized by dose to visually assess dose-related changes.
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2019
- Study start1 Apr 2019
- Primary completion11 Mar 2021
- Study completion11 Mar 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ulcerative ColitisStudies of the same condition, open and under way.
- More trials run by University of ZurichThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Patients will be randomized into two treatment arms, active ingredient or placebo with the ratio 2:1.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Zurich
- Sponsor type
- University, hospital or other
- Collaborators
- Swiss National Science Foundation, The Broad Foundation
- Responsible party
- Sponsor
- Investigators
- Gerhard Rogler, Prof. Dr. med. Dr. phil., Study director, Universitätsspital Zürich
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04000139
- Sponsor's protocol ID
- ACRE
- Acronym
- ACRE
- Status last verified
- May 2021
- First submitted
- 24 Jun 2019
- Last updated
- 11 May 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-center, Multi-national, Randomized, Double-blind, Placebo Controlled, Parallel Group, Phase IIa Study to Evaluate the Efficacy, Safety and Tolerability of an Anthocyanin-rich Extract (ACRE) in Patients With Ulcerative Colitis
- ClinicalTrials.gov ID
- NCT04000139
- Acronym / sponsor ID
- ACRE / ACRE
- Conditions
- Ulcerative Colitis
- Keywords
- bilberry, anthocyanin, anthocyanin-rich extract, ulcerative colitis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- University of ZurichUniversity, hospital or other
- Collaborators
- Swiss National Science Foundation, The Broad Foundation
- Study start
- 1 Apr 2019 (actual)
- Primary completion
- 11 Mar 2021 (actual)
- Study completion
- 11 Mar 2021 (actual)
- First posted
- 27 Jun 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study evaluates the efficacy and safety of a bilberry derived anthocyanin-rich extract in patients with ulcerative colitis. Two thirds of participants will receive the anthocyanin-rich extract, while one third will receive placebo, for 8 weeks of treatment.
Detailed description
For anthocyanins (ACs), a wide range of protective biological effects have been described, such as anti-oxidative, anti-carcinogenic, anti-microbial and anti-inflammatory activities. Various research groups could identify a beneficial effect of ACs in IBD and intestinal inflammation.
A total of 112 subjects will be randomized. Subjects will be screened for eligibility between 0 and 28 days prior to baseline visit. At the baseline visit, subjects with moderate to severe ulcerative colitis (Mayo score ≥6) and fulfilling all inclusion/exclusion criteria will be randomized into two treatment arms (ACRE or placebo). Total duration of drug product administration will be 8 weeks (56 days) followed by a follow-up phase of 30 days.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Patients will be randomized into two treatment arms, active ingredient or placebo with the ratio 2:1.
| Arm | Type | Receives |
|---|---|---|
| Standardized anthocyanin rich extract | Active comparator | Drug: Standardized anthocyanin-rich extract3 doses of 2x 500mg in capsules daily |
| Placebo | Placebo comparator | Drug: Placebo3 doses of 2x 500mg in capsules daily |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Male or female ≥ 18 years of age
- Established diagnosis of UC, with minimum time from diagnosis of ≥3 months
- Moderately at least left sided UC (disease should extend 15 cm or more above the anal verge). Disease severity determined by a Modified Mayo score of 6 to 12 with an endoscopic sub score ≥2 assessed by central reading of endoscopy performed at screening visit and no other individual sub score <1 (see 9.8.2 for more detailed information)
- Current oral or rectal 5-ASA/SP use or a history of oral or rectal 5-ASA/SP use
- Current steroids use or history of steroids dependency, refractory, or intolerance, including no steroids treatment due to earlier side-effects (only one of the steroids criteria have to be fulfilled, see definition in European Crohn´s and Colitis organization (ECCO) guidelines)
Key exclusion criteria (33 listed)
- Subjects fulfilling any of the following criteria are not eligible for inclusion in this study:
- Suspicion of differential diagnosis such as; Crohn's enterocolitis, ischaemic colitis, radiation colitis, indeterminate colitis, infectious colitis, diverticular disease, associated colitis, microscopic colitis, massive pseudopolyposis or non-passable stenosis
- Acute fulminant UC and/or signs of systemic toxicity
- UC limited to the rectum (disease which extends <15 cm above the anal verge)
- History of malignancy, except for:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Standardized anthocyanin-rich extract3g of anthocyanin-rich extract taken daily as: 3 doses of 2x 500mg. Treatment duration 56 days (8 weeks). | Drug | Standardized anthocyanin rich extract |
| Placebo3g of placebo taken daily as: 3 doses of 2x 500mg. Treatment duration 56 days (8 weeks). | Drug | Placebo |
Primary outcome
Clinical response at week 8
Time frame: 8 weeks
Proportion of patients with clinical response at week 8 where clinical response is defined as the reduction of total mayo score ≥ 3 points
13 secondary outcomes
Clinical remission at week 8
Time frame: 8 weeks
Rectal bleeding
Time frame: 8 weeks
Stool frequency
Time frame: 8 weeks
Endoscopic remission
Time frame: 8 weeks
Histological remission
Time frame: 8 weeks
Symptomatic remission
Time frame: 4 weeks
Rectal bleeding week 4
Time frame: 4 weeks
Stool frequency week 4
Time frame: 4 weeks
Durable symptomatic remission
Time frame: 8 weeks / 12 weeks
Clinical response
Time frame: 8 weeks
Fecal calprotectin
Time frame: 8 weeks
Steroid dosage
Time frame: 4 weeks (follow-up phase)
SIBDQ
Time frame: 8 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 May 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gerhard Rogler, Prof. Dr. med. Dr. phil. study director
Universitätsspital Zürich
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Standardized anthocyanin-rich extract in people with Ulcerative Colitis, run by University of Zurich at 6 sites in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical response at week 8 (time frame: 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 May 2021.