Mini-MARVEL - Mitochondrial Antioxidant Therapy in Ulcerative Colitis

NCT05539625 | Withdrawn Phase 2 DMC

• 1 other identifier: AC21067
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Mini-MARVEL study, children and young people with an active flare of UC requiring either the start of or an increase in existing mesalazine therapy will be given either MitoQ or placebo as a daily capsule for 24 weeks in the Mini-MARVEL M arm of the study. Those children and young people with an active flare of UC requiring the start of an oral steroid course will be given either MitoQ or placebo as a daily capsule for 24 weeks in the Mini- MARVEL S arm of the study, Further, newly diagnosed children and young people with UC can have either MitoQ or placebo as a daily capsule for 24 weeks with their newly started mesalazine therapy in the Mini-MARVEL M arm of the study, or with their newly started oral steroid course in the Mini-MARVEL S arm of the study. This trial will look at how feasible a multi-centre stratified RCT of this add-on (adjunct) therapy in paediatric UC is in the UK. An assessment after 6, 12 and 24 weeks will be carried out to find out if MitoQ will result in higher rates of improvement in the participants' symptoms, quality of life and gut lining inflammation. Furthermore, the trial will investigate if their UC will be better controlled and that they are less likely to need further steroids or more potent forms of drugs. MitoQ has been shown to be safe in 2 large human clinical studies in Parkinson's disease and Hepatitis C, but the Mini-MARVEL study, starting alongside the adult MARVEL study, will be the first study in UC in children and young people. At low doses, MitoQ is used as a nutritional supplement that has an anti-oxidant effect. Currently, many drug treatments in UC are very strong, expensive and aimed at suppressing the immune system. Steroid courses are often needed but these have lots of adverse events in children and young people and are strongly disliked by many. If the Mini- MARVEL study provides supportive data on feasibility, including where we have to concentrate our efforts to include enough children and young people through to study end, we could design a full-scale trial to see if MitoQ can be a safe and cost-effective new treatment that works at blocking the specific inflammatory signal found in the gut lining of children and young people with UC.

Conditions

Ulcerative Colitis

Outcome Measures

Primary Outcomes (1)

• Feasibility

  Feasibility of a multi-centre placebo-controlled RCT of an add-on therapy in paediatric UC by the rate of participants recruited per centre over the 15 month recruitment period. Further feasibility parameters such as retention, , adherence and compliance, plus trial and drug acceptability will be assessed. Secondary outcome measures include clinical response and remission at Weeks 6 and 12; and remission, response, reductions in faecal calprotectin and steroid burden, quality of life, safety and tolerance) will be determined at Week 24.

  24 weeks

Secondary Outcomes (22)

• Clincial Response

  6, 12, 24 weeks

• Clinical remission

  6, 12, 24 weeks

• Clinical response and remission

  6, 12, 24 weeks

• Difference in mean PUCAI scores at weeks 6, 12 and 24 weeks

  6, 12, 24 weeks

• Steroid-free remission rate at weeks 12 and 24

  12 and 24 weeks

Study Arms (2)

MitoQ

ACTIVE COMPARATOR

Once daily dosing of two capsules for 40mg/d (or one capsule for 20mg/d if weight \<30kgs)

Dietary Supplement: MitoQ

Placebo

PLACEBO COMPARATOR

Participants will take an oral matched placebo daily

Other: Placebo

Interventions

MitoQ DIETARY_SUPPLEMENT

MitoQ in inflammation: In the experimental setting, MitoQ has been extensively studied with clear mode of action on inflammatory mechanisms relevant to IBD: MitoQ can limit the damage to mitochondria caused by mitochondrial ROS and thereby reducing the leak and oxidisation of mtDNA that are critical to its pro-inflammatory actions within the cell. MitoQ reduces the inflammatory potential of mitochondrial DNA which have escaped or released from dying inflammatory cells. MitoQ can influence how the immune cells generate their energy, diverting it away from a more inflammatory type of metabolism (glycolysis) MitoQ can induce autophagy, a cellular recycling mechanism that removes damaged mitochondria. Defective autophagy is heavily implicated in the pathogenesis of IBD. Hence collectively, MitoQ acts upstream of several pro-inflammatory mechanisms with the net effect to promote resolution of inflammation and mucosal healing.

MitoQ

Placebo OTHER

Placebo

Placebo

Eligibility Criteria

• Age: 6 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age 6 to17 years in a PIBD service
• Able and willing to give informed consent if aged 16-17 years of age; parents or guardian able and willing to give informed consent if a child of age 15 years and under
• Confirmed UC as documented in the medical notes
• Mild-moderate severity (PUCAI score 10-55)
• (i) If Incident (newly diagnosed) case (biopsy confirmation of suspected UC at endoscopy) or within 2 weeks of diagnosis - no anti-inflammatory medication or if started on 5-ASA on day of endoscopy for presumed UC (ii) If Prevalent case - No medication or stable dose of existing medicine (oral/topical 5-ASA for \>2 weeks at screening; thiopurine for \>4 weeks at screening)

You may not qualify if:

• Inability to swallow capsules
• Young person (16-17 years of age) with inability to provide consent due to a lack of capacity
• Crohn's disease (CD) or IBD unclassified (IBDU) as documented in the medical notes
• Evidence of acute severe UC (ASUC) - ASUC is a medical emergency in children and young people with UC who are clinically unwell with marked diarrhoea, haematochezia and abdominal pain, and by definition have a paediatric UC activity index (PUCAI) score of at least 65 points
• Physician judgement that the subject is likely to require hospitalisation for medical care or surgical intervention of any kind for UC (e.g. colectomy) within 12 weeks of baseline
• Evidence of current (or previous in last 12 months) toxic megacolon (using defined paediatric criteria - radiographic evidence of transverse colon diameter ≥56 mm (or \>40mm in those \<10 years) PLUS evidence of systemic toxicity (such as: fever \>38 degrees Celsius, tachycardia (heart rate \>2 SD above mean for age), dehydration, electrolyte disturbance (sodium, potassium or chloride), altered level of consciousness, coma, hypotension or shock) or bowel perforation
• Infective colitis in UC (C\&S, C. difficile toxin positive or virology at screening)
• Proctitis (inflammation confined to the rectum, with no proximal extension to the sigmoid) for incident cases after colonoscopy or prevalent cases at most recent colonoscopy
• UC with Primary Sclerosing Cholangitis (PSC) - PSC is a chronic disease characterized by inflammation and scarring of the bile ducts resulting in strictures of the biliary tree; most cases in children are associated with IBD. The diagnosis is made by liver imaging with MRI/MRCP.
• Age \<18 years but in adult IBD service
• Intravenous corticosteroids for treatment of colitis within 8 weeks of screening
• Current or previous exposure to tacrolimus, cyclosporin, or mycophenolate,
• Current or previous exposure to biological therapy (anti-TNF, vedolizumab or ustekinumab) and oral JAK-inhibitors (tofacitinib)
• Subjects with current barriers in language or communication that in the judgement of local PI will impede the completion of the trial.
• Female patient with child-bearing potential who does not wish to use a medically acceptable method of contraception throughout the treatment period and for 1 month after discontinuation of treatment. (Appropriate methods of contraception include IUD, oral contraceptive, subdermal implant and double barrier (condom with a contraceptive sponge or contraceptive pessary)

Sponsors & Collaborators

• University of Edinburgh: lead
• The Jon Moulton Charity Trust: collaborator
• MitoQ: collaborator

Study Sites (1)

NHS Lothian

Edinburgh, United Kingdom

Location

MeSH Terms

Conditions

Colitis, Ulcerative

Interventions

mitoquinone

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 4, 2022
• First Posted: September 14, 2022
• Study Start: September 1, 2025
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): October 31, 2026
• Last Updated: January 9, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)