Maintaining the integrity of muscle during hospitalisation in older persons with severe acute exacerbation of chronic obstructive pulmonary disease (MINT-COPD)
| ISRCTN | ISRCTN14321370 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN14321370 |
| ClinicalTrials.gov (NCT) | Nil known |
| Clinical Trials Information System (CTIS) | Nil known |
| Integrated Research Application System (IRAS) | 1010818 |
| Protocol serial number | 1043, CPMS 64399 |
| Sponsor | University of Leicester |
| Funder | Wellcome Leap |
- Submission date
- 24/01/2025
- Registration date
- 09/04/2025
- Last edited
- 25/09/2025
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Respiratory
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
Contact information
Scientific, Principal investigator
NIHR Leicester Biomedical Research Centre – Respiratory
University Hospitals of Leicester NHS Trust
Glenfield Hospital
Leicester
LE3 9QP
United Kingdom
| Phone | +44 (0)116 258 3663 |
|---|---|
| neil.greening@leicester.ac.uk |
Public
NIHR Leicester Biomedical Research Centre – Respiratory
University Hospitals of Leicester NHS Trust
Glenfield Hospital
Leicester
LE3 9QP
United Kingdom
| Phone | +44 (0)116 258 3370 |
|---|---|
| mint-copd@leicester.ac.uk |
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Double-blind randomized placebo-controlled parallel-group trial |
| Secondary study design | Randomised controlled trial |
| Study type | Participant information sheet |
| Scientific title | A Phase IIa randomised, double-blind, placebo-controlled trial of RJx-01 to maintain the integrity of muscle during hospitalisation in older persons with severe acute exacerbation of chronic obstructive pulmonary disease |
| Study acronym | MINT-COPD |
| Study objectives | Primary objective: To evaluate the safety and tolerability of RJx-01 compared with placebo, between day 1 and day 197 following hospitalisation with an exacerbation of COPD (AECOPD). Exploratory objectives: To establish the effect of RJx-01 on muscle function, strength, mass, fatigability, and cellular and molecular dynamics, as well as exploratory safety, tolerability, and pharmacokinetics. Additionally, the study will assess its impact on frailty status, physical activity, health-related quality of life, fatigue, cognition, mortality, and healthcare utilisation following hospitalisation with an AECOPD, compared with placebo |
| Ethics approval(s) |
Approved 28/03/2025, East Midlands - Leicester Central Research Ethics Committee (2 Redman Place, Stratford, London, E20 1JQ, United Kingdom; +44 (0)207 104 8066, +44 (0)207 104 8227, +44 (0)207 104 8284; leicestercentral.rec@hra.nhs.uk), ref: 25/EM/0032 |
| Health condition(s) or problem(s) studied | Chronic obstructive pulmonary disease (COPD) |
| Intervention | Participants will be randomised using an online randomisation software to receive either IMP (RJx-01) or placebo once daily (OD) for 168 days (~6 months). Stratification criteria will be applied during randomisation and will include pre-admission clinical frailty score (CFS) score (≤4, >4) and sex (male/female). Dosing will begin during hospital admission. Details of dosage and dosing schedule are detailed below: IMP: The active IMP consists of minitablets containing both metformin (MET) and galantamine (GAL) as active ingredients. Following 7 days of continuous treatment, the dose will be titrated from 320 mg MET/ 6 mg GAL per day (equivalent to 150 minitablets MET and 6 minitablets GAL per day) to 960 mg MET / 12 mg GAL per day (equivalent to 450 minitablets MET and 12 minitablets GAL per day). Placebo: The placebo consists of minitablets containing placebo MET and GAL, with 0 mg of drug substance. The placebo minitablets are visually indistinguishable from the IMP and contain the equivalent number of minitablets for each phase of administration. Participants will be followed up with safety and exploratory outcomes measured before discharge and on days 8, 29, 57, 85, 113, 141, 169, and 197 (safety follow-up), as well as during any subsequent hospital admission(s). Other than the intervention described, all other care will be standard medical care delivered by the relevant clinical team. |
| Intervention type | Drug |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | RJx-01 [metformin hydrochloride, galantamine hydrobromide] |
| Primary outcome measure(s) |
Current primary outcome measures as of 25/09/2025: |
| Key secondary outcome measure(s) |
Current secondary outcome measures as of 25/09/2025: |
| Completion date | 31/08/2028 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Mixed |
| Lower age limit | 55 Years |
| Sex | All |
| Target sample size at registration | 130 |
| Key inclusion criteria | 1. Symptoms typical of COPD when stable, defined as all of: 1.1. Baseline extended MRC dyspnoea grade ≥3 when stable 1.2. FEV1/FVC ratio <0.7 (only if previous spirometry available) 1.3. Usually on maintenance inhaled therapy for COPD (any of long-acting muscarinic antagonist [LAMA], Long-acting beta-agonist [LABA] +/- Inhaled Corticosteroid [ICS]) 2. A clinician defined acute exacerbation of COPD (AECOPD) requiring admission to hospital and change in treatment (e.g. addition of systemic corticosteroids +/- antibiotics) 3. Able to initiate the first dose of the IMP when medically fit for discharge from hospital 4. Current or ex-smoker with cumulative smoking history ≥10 pack years 5. Age ≥55 years at time of screening 6. Predicted length of hospital stay ≥48 hours 7. Willing and able to consent to participate in the trial 8. Able to understand written and spoken English to a level so able to complete study measures, or with support from English-speaking family 9. If male with a partner who is a woman of childbearing potential (WOCBP), then willingness to comply with protocol contraception requirements (section 10.9) Sub-study inclusion criteria 1. Meets eligibility criteria and has consented to participate in the COPD-MINT main trial 2. Willing and able to consent to participate in the sub-study |
| Key exclusion criteria | Current exclusion criteria as of 25/09/2025: 1. Use of any antidiabetic medication (including Metformin), any acetylcholinesterase inhibitor (AChE-I) medication (including Galantamine), or any systemic medication with significant cholinergic or anticholinergic effects within 6 months prior to screening or during the study period, except for long-acting muscarinic antagonist (LAMA) inhalers. 2. Patients with known hypersensitivity to MET, GAL or any excipients used in the formulations, including tartrazine (FD&C yellow number 5) 3. Hospital admission within the 2 weeks prior to the first day of current hospital admission. 4. ≥3 emergency/unplanned hospital admissions in the previous 6 months. 5. Unstable or life-threatening cardiac disease, including myocardial infarction or unstable angina in the previous 12 months (added 02/07/2025: excluding Type 2 myocardial infarction). 6. Unstable or life-threatening cardiac arrhythmia requiring intervention in the previous 3 months, QTc >500 msec or 2nd or 3rd degree Bundle Branch block, or subjects who are at increased risk of QTc prolongation in the view of the investigator including due to concurrent use of multiple medications known to increase the risk of QTc prolongation. 7. Clinical evidence of congestive cardiac failure as the primary cause of dyspnoea or physical limitation. 8. Normally bed-bound (Clinical Frailty Score 8 or higher). 9. Women of childbearing potential (WOCBP) or those who are currently pregnant or breastfeeding 10. Patients whose treatment is considered palliative due to a condition other than COPD (life expectancy <3 months). 11. Anticipated prolonged delay to hospital discharge due to social (non-medical) issues. 12. Other conditions including current diabetes mellitus, active cancer, interstitial lung disease, primary pulmonary hypertension, significant circulatory dysfunction (e.g., acute heart failure, sepsis, shock, severe dehydration), chronic liver disease, drug and/or alcohol abuse or any other conditions that in the view of the investigator will affect the trial. 13. Participation in an interventional clinical trial within 3 months of screening or receipt of any investigational medicinal product within 3 months or 5 half-lives. 14. Evidence of hepatic insufficiency, defined as ALT or AST levels greater than 3 times the upper limit of normal. 15. Severe Renal Impairment with CrCl <30 ml/min (by Cockcroft-Gault Equation). 16. Concomitant or recent treatment with any prescription drug (<3 months) or nonprescription treatment (<2 weeks) known to affect muscle mass (e.g., with anabolic or catabolic effects), including testosterone replacement treatment, anti-androgens (such as LHRH agonists), anti-oestrogens (tamoxifen, etc.), recombinant growth hormone, Megestrol, etc. 17. Participants taking >20 mg/day oral prednisolone (or equivalent systemic corticosteroid dose) consistently for >28 days prior to screening. 18. Concomitant or recent treatment (<3 months) with an immunosuppressant agent (e.g. Disease-modifying antirheumatic drugs or monoclonal antibodies, with the exception of corticosteroids). Sub-study exclusion criteria: 1. Impaired blood clotting (family or medical history of impaired blood clotting, e.g., haemophilia) 2. Current use of warfarin, therapeutic doses of low molecular weight heparin* or any direct oral anti-coagulant (DOAC) drugs (including but not limited to betrixaban, apixaban, edoxaban, rivaroxaban, dabigatran) 3. Current use of antiplatelet agents (other than aspirin at a dose <75 mg/day) * Defined as enoxaparin >40 mg / day; tinzaparin >50 IU / kg / day; dalteparin sodium >5000 IU / day Previous exclusion criteria: 1. Use of any antidiabetic medication (including Metformin), any acetylcholinesterase inhibitor (AChE-I) medication (including Galantamine), or any systemic medication with significant cholinergic or anticholinergic effects within 6 months prior to screening or during the study period, except for long-acting muscarinic antagonist (LAMA) inhalers. 2. Patients with known hypersensitivity to MET, GAL or any excipients used in the formulations, including tartrazine (FD&C yellow number 5) 3. Hospital admission within the 4 weeks prior to the first day of current hospital admission. 4. ≥4 emergency/unplanned hospital admissions in the previous 12 months. 5. Unstable or life-threatening cardiac disease, including myocardial infarction or unstable angina in the previous 12 months (added 02/07/2025: excluding Type 2 myocardial infarction). 6. Unstable or life-threatening cardiac arrhythmia requiring intervention in the previous 3 months, QTc >500 msec or 2nd or 3rd degree Bundle Branch block. 7. Clinical evidence of congestive cardiac failure as the primary cause of dyspnoea or physical limitation. 8. Normally bed-bound (Clinical Frailty Score 8 or higher). 9. Women of childbearing potential (WOCBP) or those who are currently pregnant or breastfeeding 10. Patients whose treatment is considered palliative due to a condition other than COPD (life expectancy <3 months). 11. Anticipated prolonged delay to hospital discharge due to social (non-medical) issues. 12. Other conditions including current diabetes mellitus, active cancer, interstitial lung disease, primary pulmonary hypertension, significant circulatory dysfunction (e.g., acute heart failure, sepsis, shock, severe dehydration), chronic liver disease, drug and/or alcohol abuse or any other conditions that in the view of the investigator will affect the trial. 13. Participation in an interventional clinical trial within 3 months of screening or receipt of any investigational medicinal product within 3 months or 5 half-lives. 14. Evidence of hepatic insufficiency, defined as ALT or AST levels greater than 3 times the upper limit of normal. 15. Severe Renal Impairment with CrCl <30 ml/min (by Cockcroft-Gault Equation). 16. Concomitant or recent treatment with any prescription drug (<3 months) or nonprescription treatment (<2 weeks) known to affect muscle mass (e.g., with anabolic or catabolic effects), including testosterone replacement treatment, anti-androgens (such as LHRH agonists), anti-oestrogens (tamoxifen, etc.), recombinant growth hormone, Megestrol, etc. 17. Participants taking >20 mg/day oral prednisolone (or equivalent systemic corticosteroid dose) consistently for >28 days prior to screening. 18. Concomitant or recent treatment (<3 months) with an immunosuppressant agent (e.g. Disease-modifying antirheumatic drugs or monoclonal antibodies, with the exception of corticosteroids). Sub-study exclusion criteria: 1. Impaired blood clotting (family or medical history of impaired blood clotting, e.g., haemophilia) 2. Current use of warfarin, therapeutic doses of low molecular weight heparin* or any direct oral anti-coagulant (DOAC) drugs (including but not limited to betrixaban, apixaban, edoxaban, rivaroxaban, dabigatran) 3. Current use of antiplatelet agents (other than aspirin at a dose <75 mg/day) * Defined as enoxaparin >40 mg / day; tinzaparin >50 IU / kg / day; dalteparin sodium >5000 IU / day |
| Date of first enrolment | 12/05/2025 |
| Date of final enrolment | 31/08/2026 |
Locations
Countries of recruitment
- United Kingdom
- England
Study participating centre
Groby Road
Leicester
LE3 9QP
United Kingdom
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|---|
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| IPD sharing plan | The data-sharing plans for the current study are unknown and will be made available at a later date |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
| Study website | Study website | 11/11/2025 | 11/11/2025 | No | Yes |
Editorial Notes
25/09/2025: The exclusion criteria, primary and secondary outcome measures were updated.
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.
