E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
decreased exercise capacity |
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E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065629 |
E.1.2 | Term | Decreased exercise endurance |
E.1.2 | System Organ Class | 100000004867 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective will be to see if Allopurinol can improve tiredness in the legs after exercise. To measure this we will be assessing the rate of metabolism (how quickly or efficiently the leg muscle uses up energy) before, during and after exercising leg muscles and using an MRI machine to measure this. |
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E.2.2 | Secondary objectives of the trial |
There are a number of secondary objectives all designed to assess the effects of allopurinol on functional impairment. Namely how far the participant can walk in 6 minutes and on a short battery of exercise tests before and after a 20 week course of allopurinol or placebo
• To assess the effect of allopurinol on the health of blood vessels walls elasticity (healthy blood vessels are more elastic than unhealthy one which stiffen up) and blood markers which indicate the health of blood vessels, how well the participant uses energy and how well their muscle metabolises oxygen.
The study will also assess the effect of allopurinol on Quality of Life as measured by a short questionnaire
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Age 65 and over • 6-Minute Walk Distance less than 400m
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E.4 | Principal exclusion criteria |
-Documented history of peripheral arterial disease -Pre-existing diagnosis of severe heart failure (LVEF<35%) -Malignancy under active treatment (excluding basal cell carcinoma) -Severe COPD (Physician diagnosis) -Intolerance to allopurinol -On long term high dose steroids (eq. Prednisolone>10mg/day due to risk of steroid induced myopathy and osteoporosis) -Immobility that would render the patient incapable of doing the Short Physical Performance Battery Test (SPPB) or 6MWT -Patients who have participated in any other clinical drug trial within the previous 30 days will be excluded -Cognitive impairment precluding informed consent -Patients with active acute gout -Patients who have had allopurinol in the previous 30 days or those on long-term allopurinol -Patients with chronic kidney disease with an eGFR of 30ml/ or less -Patients who have contraindications to MRS scanning As the leg is the only part of the body in the scanner (unlike traditional MRI) we will not specifically exclude patients who have claustrophobia. Should they still not wish to take part, this is covered under the exclusion criteria: “Any other considered by a study physician to be inappropriate for inclusion” -Patients who are allergic or contraindicated to GTN should be excluded from undertaking FMD -Any other considered by a study physician to be inappropriate for inclusion
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome is to determine if allopurinol improves the initial rate of Phosphocreatine (PCr) recovery (ViPCr) in patients with impaired functional ability as measured by MRI, compared to placebo. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• Change in forearm blood flow: measured by Flow Mediated Dilatation (FMD) • 6-Minute Walk Test- a measure of walking physical performance o Short Physical Performance Battery (SPPB) test-a brief validated measure of functional performance (gait speed, balance, chair stands) that is outcome measure of choice for trials to improve physical function in older people, and has been proposed to the FDA as a surrogate licensing marker • Health-related quality of life, measured using the EuroQoL, EQ-5D questionnaire • Lean body mass, measured using bioimpedance (Tanita 101 BIA machine) o F2-Isoprostanes and 8-OHdG – circulating biomarkers of oxidative stress (lipid peroxidation and oxidative DNA damage respectively) o Muscle Biopsy markers: TBARS, 4HE conjugation, and carbonylation, ATP, PCr, creatine, free ADP,AMP concentration and lactate assays o Post-exercise muscle perfusion: measured by Arterial spin labelling (ASL) using MR Spectroscopy • Muscle ADP level: measured by Pi/PCr ratio via MR Spectroscopy
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Timepoint for all above secondary outcome measures is 20 weeks |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Information not present in EudraCT |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 30 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 30 |