Anthocyanin Rich Extract (ACRE) in Patients With Ulcerative Colitis

• Register: ClinicalTrials.gov
• Last refreshed on: 24 May 2021
• Main ID: NCT04000139
• Date of registration: 24/06/2019
• Prospective Registration: No
• Primary sponsor: University of Zurich
• Public title: Anthocyanin Rich Extract (ACRE) in Patients With Ulcerative Colitis ACRE
• Scientific 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
• Date of first enrolment: April 1, 2019
• Target sample size: 48
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT04000139
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 2

Countries of recruitment

Switzerland

Contacts

• Name: Gerhard Rogler, Prof. Dr. med. Dr. phil.
• Affiliation: Universitätsspital Zürich

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Male or female = 18 years of age

2. Established diagnosis of UC, with minimum time from diagnosis of =3 months

3. 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)

4. Current oral or rectal 5-ASA/SP use or a history of oral or rectal 5-ASA/SP use

5. 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)

6. One of the following points must be fulfilled:

1. 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

2. Intolerance to oral 5-ASAs or azathioprine OR

3. 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.

7. Allowed to receive a therapeutic dose of following UC drugs during the study:

1. Oral steroids therapy (=30 mg prednisone or equivalent/daily) providing that the
dose has been stable for 2 weeks prior Baseline

2. Oral or rectal MMX Budesonide therapy (9mg/daily) initiated and a stable dose at
least 2 months before Baseline

3. 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.

4. 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

5. 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

6. 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

8. Ability to understand the treatment, willingness to comply with all study requirements
and ability to provide informed consent

Exclusion Criteria:

Subjects fulfilling any of the following criteria are not eligible for inclusion in this
study:

1. 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

2. Acute fulminant UC and/or signs of systemic toxicity

3. UC limited to the rectum (disease which extends <15 cm above the anal verge)

4. History of malignancy, except for:

1. Treated (cured) basal cell or squamous cell in situ carcinoma

2. Treated (cured) cervical intraepithelial neoplasia or

3. carcinoma in situ of the cervix with no evidence of recurrence within the
previous 5 years prior to the screening visit

5. 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

6. 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)

7. Serious active infection

8. Gastrointestinal infections including positive Clostridium difficile stool assay

9. Currently receiving parenteral nutrition or blood transfusions

10. Females who are lactating or have a positive serum pregnancy test during the screening
period

11. 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

12. Subjects who have been treated with

a. A dose of = 1 mg per kg body weight prednisone or =30mg/d in the last 4 weeks prior
to randomization.

13. 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.

14. known history of alcohol abuse, chronic liver or biliary disease

15. Repeated and confirmed laboratory findings showing:

1. total bilirubin greater than 2 x upper limit of the normal range (ULN) unless in
context of Gilbert's syndrome

2. alkaline phosphatase (AP) greater than 2 x ULN

3. ALT (SGPT) greater than 2 x ULN

4. serum creatinine greater than 2 X ULN

5. 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.

6. platelet count <100,000/µL

7. Hemoglobin less 8 g/dL and/or other signs of severe anemia.

16. History or presence of a significant renal disease.

17. 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.

18. Current history of active systemic bacterial, viral or fungal infections

19. 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



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Ulcerative Colitis

Intervention(s)

Drug: Standardized anthocyanin-rich extract

Drug: Placebo

Primary Outcome(s)

Clinical response at week 8 [Time Frame: 8 weeks]

Secondary Outcome(s)

SIBDQ [Time Frame: 8 weeks]

Fecal calprotectin [Time Frame: 8 weeks]

Stool frequency [Time Frame: 8 weeks]

Clinical response [Time Frame: 8 weeks]

Endoscopic remission [Time Frame: 8 weeks]

Clinical remission at week 8 [Time Frame: 8 weeks]

Durable symptomatic remission [Time Frame: 8 weeks / 12 weeks]

Histological remission [Time Frame: 8 weeks]

Stool frequency week 4 [Time Frame: 4 weeks]

Rectal bleeding [Time Frame: 8 weeks]

Rectal bleeding week 4 [Time Frame: 4 weeks]

Symptomatic remission [Time Frame: 4 weeks]

Steroid dosage [Time Frame: 4 weeks (follow-up phase)]

Secondary ID(s)

ACRE

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Swiss National Science Foundation

The Broad Foundation