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Contact the study team using the details below to take part. If there are no contact details below please ask your doctor in the first instance.

Contact Information:

Prof Melanie Davies
melanie.davies@uhl-tr.nhs.uk


Dr Dimitris Papamargaritis
Dimitris.Papamargaritis@uhl-tr.nhs.uk


Prof Thomas Yates
ty20@le.ac.uk


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Be Part of Research - Trial Details - Investigating and optimising physical function with weight loss
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Investigating and optimising physical function with weight loss

Recruiting

Open to: All Genders

Age: Mixed

Loughborough Leicester Leicester

Medical Conditions

Overweight or obesity

This information is provided directly by researchers, and we recognise that it isn't always easy to understand. We are working with researchers to improve the accessibility of this information. In some summaries, you may come across links to external websites. These websites will have more information to help you better understand the study.


This study investigates different weight loss strategies for individuals living with overweight and obesity and the effect they have on people's ability to function in everyday life. The different weight loss strategies include drugs, diet and exercise. It is known that people living with overweight and obesity can find daily tasks such as standing up from a chair or lifting shopping more difficult than a person of a healthy weight. If individuals can be helped to lose weight, this might improve their ability to complete daily tasks and could improve their quality of life, as well as other health-related outcomes.

Start dates may differ between countries and research sites. The research team are responsible for keeping the information up-to-date.  

The recruitment start and end dates are as follows:

29 Jan 2025 01 Oct 2028

There are three initial cohorts:
1. Those aged between 18 and 44 years
2. Those aged between 45 and 75 years
3. Those with a diagnosis of long COVID
This is an adaptive platform trial, which means interventions may come and go depending on how well they are working. Because of this, there is no set timeline for how long the study will last. Initially, the plan is to conduct the study until September 2029. Participants will be randomised to either usual care or a weight loss intervention (one of four initially). These interventions will last for 24 weeks, with an option to continue afterwards.


Adults aged between 18 to 75 years old, with a body mass index (BMI) greater than 30 kg/m2 or a BMI between 27.0 and 30.0 kg/m2 with at least one of the weight-related risk factors (such as high blood pressure). Individuals must be able to walk without assistance and be weight stable for at least 90 days before the study starts.

You can take part if:



You may not be able to take part if:


Current exclusion criteria as of 14/10/2025:

Master Exclusion Criteria Individuals will be excluded if they meet any of the following: 1. Currently or previously (within the past 90 days before screening) participating in a weight loss intervention or group. 2. Previous or planned (during the trial period) obesity treatment with surgery or a weight loss device. However, the following are allowed: (1) liposuction and/or abdominoplasty, if performed > 1 year before screening, (2) lap banding, if the band has been removed > 1 year before screening, (3) intragastric balloon, if the balloon has been removed > 1 year before screening or (4) duodenal-jejunal bypass sleeve, if the sleeve has been removed > 1 year before screening.3. Treatment with any medication for the specific purposes of weight loss within the past 90 days before screening.4. Treatment with any GLP-1RA or DPP4 inhibitor therapies for glucose control or weight loss within the past 90 days before screening.5. Hypersensitivity or allergy to GLP-1 agonists or their excipients.6. Taking medication known to induce weight gain within the past 90 days before screening such as atypical antipsychotic and mood stabilizers7. Other weight loss or gain therapy-specific contraindications as judged by the study clinician.8. Glucocorticoid therapy (excluding topical, intraocular, intranasal, intraarticular, or inhaled preparations) within the past 90 days before screening, or have an active autoimmune abnormality that in the opinion of the trial clinician will require future treatment with systemic glucocorticoids.9. Uncontrolled thyroid disease, defined as thyroid stimulating hormone (TSH) > 6.0 mIU/L or < 0.4 mIU/L at screening (Visit 0).10. Those failing exercise screening protocol, as defined within the standard operating procedure developed by the NIHR Leicester Biomedical Research Centre (e.g., chest discomfort with exertion). 11. Currently taking bolus insulin or using an insulin pump.12. HbA1c ≥ 10% at screening (Visit 0).13. Blood pressure > 160/100 at screening (Visit 0).14. Active or untreated malignancy or in remission for less than 3 years.15. Current or planned pregnancy, or breastfeeding. Planned pregnancy in this instance involves women of childbearing potential (see definition in section 6.3) actively trying to become pregnant or aiming to become pregnant within the next six months. 16. Stage 3b CKD, defined as eGFR <30 ml/min/1.73m² at screening (Visit 0).17. Any of the following: myocardial infarction, stroke, diagnosed heart failure or arrhythmogenic cardiomyopathy, atrial fibrillation, a pacemaker or implantable cardioverter defibrillator or hospitalisation for other cardiac events within the past six months.18. Documented or self-reported liver cirrhosis.19. Current participation in another research study with investigational medical products. 20. Serious illness with life expectancy < 1 year or other significant illness or disability which, in the opinion of the principal investigator or study clinician, precludes involvement.21. Individuals with acute pancreatitis or a history of chronic pancreatitis.22. Have a history of active or unstable Major Depressive Disorder (MDD) or other severe psychiatric disorder (e.g. schizophrenia, bipolar disorder) within the last 2 years. Patients with MDD or a generalized anxiety disorder whose disease state is considered stable may be considered for inclusion if they are not on excluded medications.23. Personal or family history of Medullary Thyroid Carcinoma (MTC).24. Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). 25. Unwilling to comply with contraceptive requirements. 26. History of a serious eating disorder within the past 5 years.27. History of substance abuse within the past 5 years.28. Excessive alcohol intake as determined by liver function tests or the opinion of the trial clinician. 29. Currently undertaking more than 60 minutes a week of vigorous exercise or sport (self-reported and assessed by the investigators who will ask probing questions to ensure an accurate reflection is obtained)30. Treatment with tricyclic antidepressants that have been initiated less than 6 months before screening and/or has treatment with tricyclic antidepressants that have undergone a change in dosage or regime in the 6 months prior to screening

Cohort and sub-study(s) specific eligibility Younger age cohort Additional criteria that outline exclusion for the younger cohort: Have a confirmed clinical diagnosis of long-COVID

Middle-to-older age cohort Additional criteria that outline exclusion for the middle-to-older cohort: Have a confirmed clinical diagnosis of long-COVID

Sub-study 1Additional criteria that outline exclusion for sub-study 1: History of bleeding disorders Currently taking anti-coagulation therapy, high-dose statins, or growth hormones.

Sub-study 3Additional criteria that outline exclusion for sub-study 3: Current smoker (vaping is considered smoking in this study).

_____

Previous exclusion criteria:

Master Exclusion Criteria Individuals will be excluded if they meet any of the following: 1. Currently or previously (within the past 90 days before screening) participating in a weight loss intervention or group. 2. Previous or planned (during the trial period) obesity treatment with surgery or a weight loss device. However, the following are allowed: (1) liposuction and/or abdominoplasty, if performed > 1 year before screening, (2) lap banding, if the band has been removed > 1 year before screening, (3) intragastric balloon, if the balloon has been removed > 1 year before screening or (4) duodenal-jejunal bypass sleeve, if the sleeve has been removed > 1 year before screening.3. Treatment with any medication for the specific purposes of weight loss within the past 90 days before screening.4. Treatment with any GLP-1RA or DPP4 inhibitor therapies for glucose control or weight loss within the past 90 days before screening.5. Hypersensitivity or allergy to GLP-1 agonists or their excipients.6. Taking medication known to induce weight gain within the past 90 days before screening such as tricyclic antidepressants, atypical antipsychotics and mood stabilizers.7. Other weight loss or gain therapy-specific contraindications as judged by the study clinician.8. Glucocorticoid therapy (excluding topical, intraocular, intranasal, intraarticular, or inhaled preparations) within the past 90 days before screening, or have an active autoimmune abnormality that in the opinion of the trial clinician will require future treatment with systemic glucocorticoids.9. Uncontrolled thyroid disease, defined as thyroid stimulating hormone (TSH) > 6.0 mIU/L or < 0.4 mIU/L at screening (Visit 0).10. Those failing exercise screening protocol, as defined within the standard operating procedure developed by the NIHR Leicester Biomedical Research Centre (e.g., chest discomfort with exertion). 11. Currently taking bolus insulin or using an insulin pump.12. HbA1c ≥ 10% at screening (Visit 0).13. Blood pressure > 160/100 at screening (Visit 0).14. Active or untreated malignancy or in remission for less than 3 years.15. Current or planned pregnancy, or breastfeeding. Planned pregnancy in this instance involves women of childbearing potential (see definition in section 6.3) actively trying to become pregnant or aiming to become pregnant within the next six months. 16. Stage 3b CKD, defined as eGFR <30 ml/min/1.73m² at screening (Visit 0).17. Any of the following: myocardial infarction, stroke, diagnosed heart failure or arrhythmogenic cardiomyopathy, atrial fibrillation, a pacemaker or implantable cardioverter defibrillator or hospitalisation for other cardiac events within the past six months.18. Documented or self-reported liver cirrhosis.19. Current participation in another research study with investigational medical products. 20. Serious illness with life expectancy < 1 year or other significant illness or disability which, in the opinion of the principal investigator or study clinician, precludes involvement.21. Individuals with acute pancreatitis or a history of chronic pancreatitis.22. Have a history of active or unstable Major Depressive Disorder (MDD) or other severe psychiatric disorder (e.g. schizophrenia, bipolar disorder) within the last 2 years. Patients with MDD or a generalized anxiety disorder whose disease state is considered stable may be considered for inclusion if they are not on excluded medications.23. Personal or family history of Medullary Thyroid Carcinoma (MTC).24. Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). 25. Unwilling to comply with contraceptive requirements. 26. History of a serious eating disorder within the past 5 years.27. History of substance abuse within the past 5 years.28. Excessive alcohol intake as determined by liver function tests or the opinion of the trial clinician.

Cohort and sub-study(s) specific eligibility Younger age cohort Additional criteria that outline exclusion for the younger cohort: Have a confirmed clinical diagnosis of long-COVID

Middle-to-older age cohort Additional criteria that outline exclusion for the middle-to-older cohort: Have a confirmed clinical diagnosis of long-COVID

Sub-study 1Additional criteria that outline exclusion for sub-study 1: History of bleeding disorders Currently taking anti-coagulation therapy, high-dose statins, or growth hormones.

Sub-study 3Additional criteria that outline exclusion for sub-study 3: Current smoker (vaping is considered smoking in this study).


Below are the locations for where you can take part in the trial. Please note that not all sites may be open.

  • Loughborough University
    Epinal Way
    Loughborough
    LE11 3TU
  • Leicester Diabetes Centre
    Leicester General Hospital NHS Trus Gwendolen Road
    Leicester
    LE5 4PW
  • Diabetes Research Centre
    University of Leicester
    Leicester
    LE1 7RH

Participants will be under the care of a doctor throughout the study and will receive close monitoring of their health. If they are allocated to an intervention group, they may lose weight and feel healthier generally. There are often long-term health benefits from maintaining weight loss. The study team will review their physical function, body fat, calorie requirements, fitness levels and heart health results with them after the study is completed. By taking part in this research, participants will contribute to new scientific understanding of the health benefits of different weight loss strategies. The results could lead to improved medical treatments and programmes in the future.
Venepuncture - this will need to be performed at each of the core study visits: Visit 0 (screening and familiarisation), Visit 1 (baseline), Visit 3 (week 12), Visit 4 (week 24), Visit 5 (optional week 52) and Visit 6 (optional week104). This is to obtain the necessary blood samples. This procedure can be associated with mild to moderate pain and discomfort depending on the ease of identifying a suitable vein. The procedure will be performed by highly trained research staff using aseptic techniques and the latest devices. The comfort of the participant will be considered at all times and every attempt to make the procedure less painful (e.g. ensuring vein is identifiable by use of tourniquet, squeezing of fist, lowering forearm, putting hand in warm water). Their right to withdraw from the study or refuse the intervention will be respected at all times.
Indirect calorimetry - this will be performed using a ventilated mask device. Generally, this procedure is well tolerated. However, in a few participants, it may be associated with claustrophobia. The procedure will be clearly explained to the participant before it occurs and the right to withdraw at any time will be maintained.
Body composition will be assessed using Dual Energy X-ray Absorptiometry (DEXA) by a fully qualified technician. Although DXA uses X-rays, this is at a very low dose and any risks are negligible. Female participants under 55 years of age will be asked to have a urine pregnancy test before the scan. They will also be asked about pregnancy status and asked to sign a declaration of pregnancy status form before having a DEXA scan. Any participant at risk of being pregnant will not be scanned.
Muscle Biopsy - The administration of local anaesthetic may cause mild discomfort, and there is a small risk of haemorrhage or infection at the site of the biopsy. The area may ache for a few hours afterwards (painkillers will be available). In some cases, it can cause bleeding and bruising that can last several weeks and may restrict mobility and the ability to drive. Following the local anaesthetic the procedure is not painful, though the site of the biopsy may ache for a day. Analgesia will be offered following a biopsy. All biopsies will be performed by a doctor who has been trained and has experience with the muscle biopsy procedure.
Attendance at multiple study visits - participants will be required to attend five core study visits. All reasonable attempts will be made to ensure that attendance is not associated with too much disruption to the participant's lifestyle. Reimbursement will be provided upon receipt of a valid car parking ticket.
Participants will be arriving for the core study visits having fasted the night before, in preparation for the fasting blood tests at these core study visits. This will be following consent which will be taken at the screening visit. To ensure participant safety and avoid episodes of hypoglycaemia, the participant will be monitored closely by the clinical team on the days of the study visits they are expected to fast.
Low-energy diets can lead to symptoms like constipation, dizziness, fatigue, thirst, and/or headache in some people taking part. Trained dietitians and study clinicians will monitor participants throughout the study and will help manage side effects if they arise. These side effects tend to get better with fibre-based laxatives and time. It is also important to drink as much water as needed when on the diet.
With exercise, there are risks of injury to joints, bones, and muscles. The supervisor will work with participants to exercise as safely as possible. Exercise may also lead to fatigue and dizziness in some cases. Again, over time these should improve.
Tirzepatide is approved for weight loss, however, all medications have some unwanted side effects. Not everybody gets them, and these will be explained by the doctor before consent. The most common side effects with Tirzepatide are feeling nauseated, loose and frequent stools, throwing up, loss of appetite, indigestion, heartburn, feeling tired (fatigue), hard or infrequent stools, passing gas, bloating, belching, stomach pain or discomfort, low blood sugar and injections site reaction (such as redness, irritation, itching, swelling or rash). The study team will advise the participants to maintain adequate fluid hydration to reduce the risk of volume depletion. We will monitor participants for adverse effects and address these accordingly.

Prof Melanie Davies
melanie.davies@uhl-tr.nhs.uk


Dr Dimitris Papamargaritis
Dimitris.Papamargaritis@uhl-tr.nhs.uk


Prof Thomas Yates
ty20@le.ac.uk



The study is sponsored by University of Leicester and funded by National Institute for Health and Care Research.



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Read full details for Trial ID: ISRCTN10203365

Or CPMS 60568

Last updated 14 October 2025

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