Maintaining the integrity of muscle during hospitalisation in older persons with severe acute exacerbation of chronic obstructive pulmonary disease (MINT-COPD)

Plain English summary of protocol

Background and study aims
People living with Chronic Obstructive Pulmonary Disease (COPD) experience "flare-ups", which can result in admission to hospital and loss of muscle function. This research study is testing a new unlicensed medication called RJx-01 and aims to assess its safety and tolerability, along with its impact on muscle function and quality of life. Participants will take the medication for 6-months, starting when they are in hospital. At monthly appointments, we will conduct safety and muscle function tests.
RJx-01 is made of two medicines, metformin (used for diabetes) and galantamine (used for dementia), combined into a new treatment. Participants in this study will either receive RJx-01 or a placebo (a “dummy drug”) to compare the effects. The study will check how safe the treatment is, how well it is tolerated, and its effect on muscle health and quality of life.

Who can participate?
Patients aged 55 years and over admitted to the hospital with COPD

What does the study involve?
Participants will be randomly assigned to receive either RJx-01 or a placebo (a "dummy" treatment) in daily sachets for 168 days, starting when they leave the hospital. During this period, participants will be asked to attend monthly follow-up visits at Glenfield Hospital's Respiratory Biomedical Research Centre. At each visit, participants will receive more of their assigned treatment and have their health monitored through tests on breathing, muscle strength, body composition, blood, sputum (mucus), and urine samples.

What are the possible benefits and risks of participating?
Participation is voluntary, and participants can choose to stop at any time without affecting their standard medical care. This trial is organised by the University of Leicester and Rejuvenate Biomed, funded by the Wellcome Leap Dynamic Resilience Program. The findings will help to understand the potential of RJx-01 as a new treatment option for COPD patients to preserve muscle health and improve recovery after hospital admissions. Results will be published, but personal information will remain confidential and anonymised.
RJx-01 has already been trialled in healthy volunteers, where the treatment was well tolerated and showed a positive effect on muscle strength. However, these effects have not yet been explored in patients. The two active ingredients of RJx-01, Metformin and Galantamine, are individually licensed in the United Kingdom. Metformin has been used for decades as the first-line treatment of type 2 diabetes, and Galantamine has been used for many years for the treatment of Alzheimer’s disease. As a result, the safety of these two medications on their own is well understood.
As of October 2024, there is limited information on the safety of taking of Metformin and Galantamine together. However, product information for both Metformin and Galantamine does not restrict the use of both medications at the same time. Because they do not act on the same primary pathways in the body, it is unlikely that taking one would have a negative impact on the effects of the other.
On their own, there are risks associated with both Metformin and Galantamine. For Metformin, risks include lactic acidosis and the occurrence of gastrointestinal (GI) side effects such as diarrhea. Lactic acidosis is a very rare but serious life-threatening condition where too much lactic acid builds up in the body, leading to a drop in blood pH (acidosis). Metformin-associated lactic acidosis (MALA) can occur due to conditions like renal or liver failure, circulatory dysfunction, or an increased production of lactate from issues such as hypoxia or severe infection.
The risk for MALA occurring in study subjects is lowered by limiting the highest Metformin dose to 960 mg/day, by excluding subjects with renal or hepatic failure and excluding those with significant circulatory dysfunction or (heart failure, sepsis, shock, severe dehydration, alcohol abuse). Participants will be closely monitored during every study visit, and study treatment will be stopped if creatinine clearance decreases to <30 mL/min, or in case of alcohol abuse, circulatory dysfunction, or tissue hypoxia (e.g., acute heart failure). In case of general anesthesia, respiratory acidosis, severe dehydration, or use of iodinated contrast agents, study treatment will be temporarily discontinued. There is no evidence or scientific rationale as to why Galantamine would increase the risk of MALA.
Risks associated with Galantamine include a slow heart rate (bradycardia) and an increase in the time it takes for the heart’s electrical system to recharge (QT-prolongation), particularly if the medication is overdosed. To limit these risks, participants will be monitored using ECG (recording of the heart’s electrical signals), with participants excluded if they show significant QT prolongation or significant heart conduction problems. Participants will also begin by taking a lower dose of Galantamine (within RJx-01), which will be increased after 1-week (up-titration) if deemed safe to do so, up to a maximum dose of 12 mg/day. The use of Galantamine and similar medications in COPD patients with dementia didn’t seem to pose any extra risks in a previous large study (Stephenson et al, 2012).
In our study, many COPD patients will be taking inhaled medications that work via similar pathways in the body to Galantamine, but these inhalers primarily target receptors in the lungs, while Galantamine works mostly in the brain, so they don’t interfere much with how Galantamine works.
For RJx-01, the risk of GI side effects will be mitigated by administering study treatment during a meal.
Beyond standard of care the participants will undergo additional blood tests, breathing tests, and an oral IMP. These are all common routine tests. The blood and sputum sampling has minimal risk and mild discomfort. We will also monitor and analyse all potential cases of anaphylaxis and major adverse cardiac events (MACE). Several physical performance measures will be conducted in this trial by a trained Exercise Physiologist, Research Doctor, or Research Nurse. Procedures for these tests will be outlined in departmental standard operating procedure (SOP) documentation, which will be reviewed by all members of the study team.
For the optional skeletal muscle biopsy (sub-study) the skin is numbed using local anaesthetic and a small incision (less than 1 cm) is made. It is usual to experience some soreness for 24 – 48 hours after the procedure. The incision shall leave a small scar of less than 1 cm in length. There may also be some bruising around the site of the biopsy, called a haematoma. This will be performed by a qualified physician with experience conducting this procedure.

Where is the study run from?
NIHR Leicester Biomedical Research Centre (UK)

When is the study starting and how long is it expected to run for?
January 2025 to August 2028

Who is funding the study?
Wellcome Leap (UK)

Who is the main contact?
1. Dr Neil Greening, neil.greening@leicester.ac.uk
2. Jill Clanchy, mint-copd@leicester.ac.uk

Study website

Contact information

Study information

Eligibility

Locations

Countries of recruitment

• England
• United Kingdom

Study participating centre

Sponsor information

University of Leicester
University/education

Research Governance Office
Research & Enterprise Division
University Road
Leicester
LE1 7RH
England
United Kingdom

Phone	+44 (0)116 3736508
Email	RGOsponsor@le.ac.uk
Website	https://le.ac.uk/research/regi/sponsorship
"ROR"	https://ror.org/04h699437

Funders

Funder type

Charity

Results and Publications

Editorial Notes

02/07/2025: The following changes were made to the study record:
1. Contact details and exclusion criteria updated.
2. The date of first enrolment was changed from 01/05/2025 to 12/05/2025.
3. Study website added.
20/05/2025: Internal review.
09/04/2025: ISRCTN received notification of combined HRA/MHRA approval for this trial on 09/04/2025.
24/01/2025: Study's existence confirmed by the HRA.