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.

Inclusion Criteria: • Active UC (Mayo of score 6 or greater with endoscopy subscore of 2 or more); or Partial Mayo Score 4-9 (e.g. without the endoscopic score)

• Baseline rectal bleeding Mayo score of 1 or more

• ≥18 years old

• Confirmed diagnosis of UC confirmed on histology and endoscopic evidence for ≥3 months prior to screening.

• Able to start taking prednisolone at the same time as the study drug/placebo

• Subjects currently receiving the following treatment for UC are eligible providing they have been on stable dose for designated period of time

  • Oral 5-ASA or sulfasalazine stable dose for at least 4 weeks prior to inclusion and during the study period.
  • Azathioprine, 6-mercaptopurine stable dose for 8 weeks prior to study.
  • Topical treatment (5-ASA or steroid based) for active UC flare including suppository and enema.

• Able and willing to give informed consent.

Exclusion Criteria:

• Severe extensive colitis as evidenced by:

  • 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 fulminant colitis, toxic megacolon or recent history of toxic megacolon within the last 6 months; or bowel perforation.
  • Evidence of acute severe UC fulfilling Truelove and Witts Criteria (>6 bloody stools/day with evidence of any of these features: tachycardia [>90bpm], fever [>37.8C], anaemia [Hb <10.5g/dl], low albumin [<30g/l]).

• Any current or previous biologic treatment including anti-TNF therapy or anti-α4β7 therapy; and oral JAK-inhibitors

• Previous treatment for UC, except those listed in the inclusion criteria.

• UC confined to proctitis (distal 15 cm or less)

• UC with Primary Sclerosing Cholangitis (PSC)

• Diagnosis of Crohn's disease or indeterminate colitis

• Pregnancy (Current or attempting to become pregnant during trial period) or breastfeeding

• Cyclosporine, mycophenolate, or tacrolimus administration within 8 weeks of screening.

• Intravenous corticosteroids for treatment of colitis within 8 weeks of screening

• Subjects with current - or recent history of - severe, progressive, or uncontrolled renal, hepatic, haematological, gastrointestinal, metabolic (including uncontrolled hypercholesterolemia), endocrine, pulmonary, cardiac, neurological disease.

• Subjects who have positive stool examinations for enteric pathogens or Clostridium difficile toxin at screening.

• Subjects with a known allergy/contraindication to MitoQ.

• Subjects currently taking any products containing Mitoquinol mesylate (Coenzyme Q10) or any products containing Coenzyme derivatives such as Coenzyme A (CoA, SCoA, CoASH). If subjects are on these products, they can enter the trial after a 7-day washout period.

• Subjects with current barriers in language or communication that in the judgement of local PI will impede the completion of the trial.

• A history of overdose or suicide, or significant active mental health problems.