PRObiotic VSL#3® for Maintenance of Clinical and Endoscopic REMission in Ulcerative Colitis

NCT03415711 | Terminated DMC

• 1 other identifier: CDIVSL01
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) characterized by chronic inflammation limited to colonic mucosa. Its pathogenesis is not still clear, even if a multifactorial aetiology has been advocated. The aim of this study is to evaluate the long-term efficacy of two different doses of VSL#3® added on standard therapy (5-ASA) in maintaining remission in an adult population of patients with UC, compared with the standard therapy (5-ASA) plus placebo. The investigators hypothesized that adding VSL#3® to mesalamine would lead to higher remission rate at long-term evaluation.

Conditions

Ulcerative Colitis

Outcome Measures

Primary Outcomes (1)

• To characterize the efficacy of VSL#3® plus standard therapy (5-ASA) in maintaining clinical and endoscopic remission in patients with UC in remission.

  Proportion of subjects in clinical and endoscopic remission at month 12 as defined by Total Mayo Score ≤2 with no individual subscore\>1 and rectal bleed subscore of 0.

  12 months

Study Arms (3)

Mesalamine plus high-probiotic preparation VSL#3®

EXPERIMENTAL

Mesalamine 2.4 g/day in once daily administration plus VSL#3® 450 billion sachets, two sachets per day (900 billion of bacteria per day) for 12 months.

Dietary Supplement: VSL#3®; Drug: Mesalamine

Mesalamine plus low-probiotic preparation VSL#3®

EXPERIMENTAL

Mesalamine 2.4 g/day in once daily administration plus VSL#3® 450 billion sachets, two sachets twice a day (1800 billion of bacteria per day) for 12 months.

Dietary Supplement: VSL#3®; Drug: Mesalamine

Mesalamine plus Placebo

ACTIVE COMPARATOR

Mesalamine 2.4 g/day in once daily administration plus placebo for 12 months.

Drug: Mesalamine; Drug: Placebo

Interventions

VSL#3® DIETARY_SUPPLEMENT

VSL#3® 450 billion sachets

Mesalamine plus high-probiotic preparation VSL#3®; Mesalamine plus low-probiotic preparation VSL#3®

Mesalamine DRUG

Mesalamine 2.4 g/day in once daily administration.

Mesalamine plus Placebo; Mesalamine plus high-probiotic preparation VSL#3®; Mesalamine plus low-probiotic preparation VSL#3®

Placebo DRUG

sachets with maltose, cornstarch and dioxide

Also known as: Placebo (for VSL#3®)

Mesalamine plus Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Evidence of a personally signed and dated informed consent document indicating that the subject (or a legal representative) has been informed of all pertinent aspects of the study.
• Subjects are willing and able to participate in the study, complete subject assessments, attend scheduled clinic visits, and comply with all protocol requirements as evidenced by written informed consent.
• Male and/or female subjects aged ≥18 years at the time of informed consent.
• A diagnosis of UC for ≥3 months. A biopsy report must be available to confirm the histological diagnosis in the subject's source documentation. In addition, a report documenting disease duration and extent of disease (e.g., proctosigmoiditis, left-sided colitis and pancolitis) based upon prior colonoscopy must also be available in source documentation.
• Must have history of previous mild-to-moderate active disease beyond the rectum (\>15 cm from the anal verge).
• Must have UC in remission with a Total Mayo Score ≤2 with no individual subscore\>1 and rectal bleed subscore of 0.
• Must be on maintenance treatment with oral mesalamine (\<2.5 g/day), sulfasalazine (\<3.0 g/day) or olsalazine (\<1.5 g/day) on a stable dose for at least 2 weeks before randomization.
• Male and female subjects of childbearing potential must agree to avoid pregnancy throughout the duration of the study (defined as the time of the signing of the informed consent through the conclusion of subject participation). A subject is of childbearing potential if, in the opinion of the investigator, he/she is biologically capable of having children and is sexually active.
• Women of childbearing potential (WOCBP) must have a negative urine pregnancy test result at screening. WOCBP are defined as women who are biologically capable of becoming pregnant, including women who are using contraceptives or whose sexual partners are either sterile or using contraceptives.
• Women of non-childbearing potential (WONCBP) do not require a urine pregnancy test and must meet at least one of the following criteria:
• Have undergone hysterectomy or bilateral oophorectomy;
• Have medically confirmed ovarian failure or are medically confirmed to be post-menopausal (cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; laboratory confirmation of Follicle-stimulating hormone (FSH) level may be indicated if subject has history of amenorrhea for ≥ 52 weeks).
• Are medically confirmed to be post-menopausal (cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; laboratory confirmation of FSH level may be indicated if subject has history of amenorrhea for ≥ 52 weeks).

You may not qualify if:

• Subjects with a diagnosis of indeterminate colitis or Crohn's disease. Subjects with clinical findings suggestive of Crohn's disease, e.g., fistulae or granulomas on biopsy are also excluded.
• Subjects with colonic dysplasia or neoplasia.
• Subjects with a history of colonic or small bowel obstruction or resection, except for appendectomy.
• Use of rectal 5-aminosalicylic acid or systemic or rectal corticosteroids within 30 days before baseline, use of immunosuppressive agents within 12 weeks before baseline.
• Use of antitumor necrosis factor (anti-TNFα) or anti-integrin therapy for UC at any moment of previous patient history 6. Repeated use of non-steroidal anti-inflammatory drugs (NSAIDs), including the non-steroidal anti-inflammatory drugs such as aspirin or ibuprofen (except for prophylactic use of a stable dose of aspirin up to 325 mg / day for cardiac disease). Occasional use of NSAIDs is permitted.
• \. Subjects who had received another investigational agent within 30 days before baseline.
• \. Any major illness/condition or evidence of an unstable clinical condition (eg, renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, immunologic, or local active infection/infectious illness) that, in the investigator's judgement will substantially increase the risk to the subject if he or she participates in the study.
• \. Women during pregnancy or lactation.

Sponsors & Collaborators

• VSL Pharmaceuticals: lead
• Actial Farmaceutica S.r.l.: collaborator

Study Sites (1)

Istituto di Medicina Interna CIC Columbus Policlinico Universitario Agostino Gemelli Università Cattolica del Sacro Cuore

Roma, 00168, Italy

Location

MeSH Terms

Conditions

Colitis, Ulcerative

Interventions

Mesalamine

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Inflammatory Bowel Diseases; Colonic Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

meta-Aminobenzoates; Aminobenzoates; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Aminosalicylic Acids; Salicylates; Hydroxybenzoates; Hydroxy Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenols

Study Officials

• Alessandro Armuzzi

  Policlinico Universitario Agostino Gemelli Università Cattolica del Sacro Cuore

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 5, 2018
• First Posted: January 30, 2018
• Study Start: April 28, 2017
• Primary Completion: April 24, 2019
• Study Completion: April 24, 2019
• Last Updated: January 18, 2020

Record last verified: 2020-01

Locations

IT (1)