Nicotinamide Riboside and Mitochondrial Biogenesis

NCT03432871 | Completed

• 1 other identifier: A094351
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Mitochondrial Diseases; Mitochondrial Myopathies; Progressive External Ophthalmoplegia; Progressive Ophthalmoplegia; Progressive; Ophthalmoplegia, External; Mitochondria DNA Deletion; MELAS

Keywords

Mitochondria; Mitochondrial disease; Nicotinamide Riboside; Niagen; PEO; Single deletion; mtDNA deletion; MELAS; m.3243A>G

Outcome Measures

Primary Outcomes (9)

• 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

• Safety - Incidence of treatment related adverse events

  Observation over 24 hours after Nicotinamide Riboside administration. Recording of any adverse events or reactions

  24 hours

• Safety - change in blood analytes

  Change from baseline in safety blood analyte levels - CK, Creatinine, Alanine Transaminase, Aspartate Transaminase (Units U/L)

  24 hours

• 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

• 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

• 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

• 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

• 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

• 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 Outcomes (4)

• Impact on mitochondrial disease symptoms - Dynamometric measure of muscle strength

  4 weeks

• Impact on mitochondrial disease symptoms - 6-minute walk

  4 weeks

• Impact on mitochondrial disease symptoms - Quality of life (SF36 - qualitative)

  4 weeks

• Impact on mitochondrial disease symptoms - Timed get-up-and-go.

  4 weeks

Study Arms (1)

Nicotinamide Riboside

EXPERIMENTAL

This is an open-label experimental medicine study. All subjects will receive the same dosage of the supplement Nicotinamide Riboside.

Dietary Supplement: Nicotinamide Riboside

Interventions

Nicotinamide Riboside DIETARY_SUPPLEMENT

Nicotinamide Riboside is a member of the Vitamin B family which acts as a precursor to NAD+, an enzyme involved in energy production.

Also known as: Niagen, Nicotinamide Riboside Chloride

Nicotinamide Riboside

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Clinical and genetic diagnosis of:
• Progressive external ophthalmoplegia (PEO), caused by a single deletion of mitochondrial DNA
• Mitochondrial disease caused by the m.3243A\>G or A\>T mutation in mitochondrial DNA
• Age 18-70 years
• Signed informed patient consent

You may not qualify if:

• 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

Sponsors & Collaborators

• Cambridge University Hospitals NHS Foundation Trust: lead
• University of Cambridge: collaborator
• Medical Research Council Mitochondrial Biology Unit: collaborator

Study Sites (1)

Cambridge University Hospitals NHS Foundation Trust

Cambridge, CB20QQ, United Kingdom

Location

MeSH Terms

Conditions

Mitochondrial Diseases; Mitochondrial Myopathies; Ophthalmoplegia, Chronic Progressive External; MELAS Syndrome

Interventions

nicotinamide-beta-riboside

Condition Hierarchy (Ancestors)

Metabolic Diseases; Nutritional and Metabolic Diseases; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Ophthalmoplegia; Ocular Motility Disorders; Cranial Nerve Diseases; Paralysis; Neurologic Manifestations; Eye Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Mitochondrial Encephalomyopathies; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Cerebral Small Vessel Diseases; Cerebrovascular Disorders; Vascular Diseases; Cardiovascular Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Patrick Chinnery, Prof.

  University of Cambridge

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Masking Details: Experimental medicine study (open label)
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Experimental medicine study (open label)

Study Record Dates

• First Submitted: January 23, 2018
• First Posted: February 14, 2018
• Study Start: December 8, 2017
• Primary Completion: December 31, 2022
• Study Completion: December 31, 2022
• Last Updated: July 20, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)