MARVEL: Mitochondrial Anti-oxidant Therapy to Resolve Inflammation in Ulcerative Colitis

Summary

This is a Phase 2b, multi-centered, randomized, placebo-controlled trial with treatment phase over 24 weeks.

Ulcerative Colitis (UC) is a condition that causes inflammation and ulceration of the inner lining of the rectum and colon (the large bowel). In UC, ulcers develop on the surface of the lining and these may bleed and produce mucus. Individuals with UC can become very unwell with disabling bloody diarrhoea, uncontrollable bowel habit and profound tiredness. In very severe cases, UC carry the risks of rupture of the inflamed bowel wall requiring an emergency operation to remove the colon.

The MARVEL study investigates whether MitoQ is a beneficial drug treatment for UC.

Earlier studies have shown that the inflamed UC gut lining releases 'danger signals' arising from the mitochondria. These 'danger signals' attract immune cells and make inflammation worse.

Mitochondria are the 'batteries' or 'power stations' that reside within, and provide energy for living cells. In the gut lining of individuals with UC, the mitochondria are more prone to damage that increases the release of these danger signals.

MitoQ protects the mitochondria and exerts an anti-inflammatory effect. The investigators hypothesise that MitoQ will improve UC and allow the bowels to heal properly following a disease flare.

In the MARVEL study, individuals with an active flare of UC requiring standard oral Prednisolone will be given either MitoQ or placebo as a daily capsule for 24 weeks.

The Investigators will carry out an assessment after 12 and 24 weeks to find out if MitoQ will result in higher rates of improvement in the participants' symptoms and gut lining inflammation. Furthermore, the investigators 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 MARVEL study will be the first study in UC. 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. If the MARVEL study provides supportive data, MitoQ can be a safe and cost-effective new treatment that works at blocking the specific inflammatory signal found in the gut lining of individuals with UC.

Conditions

• Ulcerative Colitis Flare

Interventions

DIETARY_SUPPLEMENT

MitoQ

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.

OTHER

Placebo

Placebo

Sponsors & Collaborators

• JP Moulton Charitable Foundation

  collaborator OTHER

• MitoQ

  collaborator UNKNOWN

• University of Edinburgh

  lead OTHER

Principal Investigators

• David Wilson, MD · NHS Lothian

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2022-05-31

Primary Completion

2025-12-14

Completion

2026-11-30

Countries

• United Kingdom

Study Locations