Mitochondrial Diseases Clinical Trial
Official title:
The Role of Nicotinamide Riboside in Mitochondrial Biogenesis
Verified date | July 2023 |
Source | Cambridge University Hospitals NHS Foundation Trust |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
Mitochondria are important parts of the cell that are responsible for producing energy. The amount of energy they produce depends on how much energy the body needs to function and this energy production can be severely impaired in people with mitochondrial disease. Symptoms of mitochondrial disease vary widely but usually involve the brain, nerves and muscles, as these are tissues that need a lot of energy. Mitochondrial disorders affect 1 in 5000 of the UK population and there is currently no cure. Some scientists think that increasing the number of mitochondria in the body (mitochondrial biogenesis) might be an effective treatment for the symptoms of mitochondrial disease. Studies carried out in mice have shown that a type of B-vitamin called Nicotinamide Riboside (NR) is able to increase the number of mitochondria, leading to increased energy and a reduction in the symptoms of mitochondrial disease. The aim of this study is to investigate if the same B vitamin, Nicotinamide Riboside, can increase energy production and reduce symptoms in humans with mitochondrial disease. The study will consist of two parts: Part 1: Participants will be given a single oral dose of Nicotinamide Riboside and the levels of NR in their bloodstream will be measured at regular intervals. This will involve a single overnight stay and simple blood tests. Part 2: This requires 6 separate visits from each participant. Each participant will undergo a series of standard tests including a muscle biopsy and an MRI scan, then they will take a course of Nicotinamide Riboside (twice daily for 4 weeks). After 4 weeks of treatment, the participants will undergo the same tests again to see if there have been any changes in response to the treatment.
Status | Completed |
Enrollment | 13 |
Est. completion date | December 31, 2022 |
Est. primary completion date | December 31, 2022 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 70 Years |
Eligibility | Inclusion Criteria: Clinical and genetic diagnosis of: - Progressive external ophthalmoplegia (PEO), caused by a single deletion of mitochondrial DNA - or - Mitochondrial disease caused by the m.3243A>G or A>T mutation in mitochondrial DNA - Age 18-70 years - Women of child-bearing age only if they are not pregnant or breast feeding at the inclusion into the study and agree not to become pregnant during the study. Female participants will undergo a pregnancy test before study commencement. - Signed informed patient consent Exclusion Criteria: - Clinically significant liver disease (e.g., cirrhosis or a history of hepatitis) - Presence of significant other neurological disorders (such as multiple sclerosis, Parkinson's disease) or major co-morbidities (such as definite cognitive impairment, psychiatric disease, heart or lung failure, orthopaedic or rheumatological disorders) - Females who are at risk of pregnancy (i.e., not using regular contraception), who are pregnant, lactating or planning pregnancy - Females taking the combined oral contraceptive pill (as oestrogens can induce mitochondrial biogenesis and interfere with study results) - For MRI - medical contraindication e.g., pacemaker, deep brain stimulator, aneurysm clip or significant claustrophobia - For biopsy - varicose veins overlying biopsy site, clinically significant lower limb oedema, active lower limb infection, use of anticoagulants or antiplatelet agents that cannot be discontinued, known bleeding diathesis |
Country | Name | City | State |
---|---|---|---|
United Kingdom | Cambridge University Hospitals NHS Foundation Trust | Cambridge |
Lead Sponsor | Collaborator |
---|---|
Cambridge University Hospitals NHS Foundation Trust | Medical Research Council Mitochondrial Biology Unit, University of Cambridge |
United Kingdom,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Bioavailability | Change in baseline levels of Nicotinamide Riboside detectable in the bloodstream of participants after a standard oral dose of the supplement (at 0, 0.5, 1, 2, 6, 12 and 24 hours) | Pharmacokinetic measure - 0, 0.5, 1, 2, 6, 12 and 24 hours post-dose | |
Primary | Safety - Incidence of treatment related adverse events | Observation over 24 hours after Nicotinamide Riboside administration. Recording of any adverse events or reactions | 24 hours | |
Primary | Safety - change in blood analytes | Change from baseline in safety blood analyte levels - CK, Creatinine, Alanine Transaminase, Aspartate Transaminase (Units U/L) | 24 hours | |
Primary | Safety - temperature | Change from baseline in patient temperature (degrees celsius, measurement at 0, 0.5, 1, 2, 6, 12 and 24 hours) | Change measures - 0, 1, 2, 3, 4, 6, 8, 24 hours post-dose | |
Primary | Safety - blood pressure | Change from baseline in patient blood pressure (mmHg, measurement at 0, 0.5, 1, 2, 6, 12 and 24 hours) | Change measures - 0, 1, 2, 3, 4, 6, 8, 24 hours post-dose | |
Primary | Safety - pulse | Change from baseline in patient pulse (bpm, measurement at 0, 0.5, 1, 2, 6, 12 and 24 hours) | Change measures - 0, 1, 2, 3, 4, 6, 8, 24 hours post-dose | |
Primary | Mitochondrial biogenesis - Magnetic Resonance Imaging | Change in in vivo measurement of mitochondrial function at the start and end of the 4 weeks of NR treatment (31P-MRS measurement of mitochondrial function - Phosphocreatine replenishment after exercise) | 4 weeks | |
Primary | Mitochondrial biogenesis - Respiratory Chain Enzyme Analysis | Change from baseline in mitochondrial function at the start and end of the 4 weeks of NR treatment (Respiratory chain enzyme analysis) | 4 weeks | |
Primary | Mitochondrial biogenesis - mitochondrial DNA quantification | Change from baseline in the amount of mitochondrial DNA at the start and end of the 4 weeks of NR treatment (mtDNA quantification) | 4 weeks | |
Secondary | Impact on mitochondrial disease symptoms - Dynamometric measure of muscle strength | Participants will be asked to complete the dynamometric measure of muscle strength test, using a hand held dynamometer, before and after treatment. Force measured in kg. | 4 weeks | |
Secondary | Impact on mitochondrial disease symptoms - 6-minute walk | Participants will be asked to complete the 6 minute walk test before and after treatment. The distance they can walk in 6 minutes will be measured in metres. | 4 weeks | |
Secondary | Impact on mitochondrial disease symptoms - Quality of life (SF36 - qualitative) | Participants will be asked to complete the SF36 (Short Form 36) Quality of life questionnaire before and after treatment. This is a standard health survey used routinely in clinical practice. | 4 weeks | |
Secondary | Impact on mitochondrial disease symptoms - Timed get-up-and-go. | Participants will be asked to complete the Timed up and go test before and after treatment. The time taken to get up from sitting to standing will be measured in seconds. | 4 weeks |
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