The Effects of Nicotinamide Riboside Supplementation on Brain NAD+/NADH Ratio and Bioenergetics

Phase 4

Terminated

Conditions: Healthy

Interventions: Drug: Nicotinamide Riboside

Registration Number: NCT03151707

Lead Sponsor: Mclean Hospital

Brief Summary: The primary aim of this study is to investigate the effects of exogenously administered nicotinamide riboside (NR) on brain NAD+/NADH ratio and bioenergetics functions in healthy individuals using phosphorus magnetic resonance spectroscopy (31P MRS) imaging.

The secondary aims are to investigate the change in brain PCr/ATP and creatine kinase enzyme rate after NR use. In addition, NAD+/NADH ratio, PCr/ATP and CK enzyme rate will be measured in the calf muscle, as secondary outcome measures.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 11

Inclusion Criteria

Age: 18-80 year-old
Male or female
Without psychiatric diagnosis according to a structured psychiatric interview (Structured Clinical Interview for DSM-V Axis I Disorders (SCID))
Without history of a psychotic disorder and/or mood disorder among parents, siblings, or children, as obtained via self-report only.

Exclusion Criteria

Significant medical or neurological illness.
Diagnosis diabetes mellitus (DM), uncontrolled hypertension (HTN), severe hypotension, coronary artery disease (CAD), metabolic syndrome, glaucoma, liver impairment, decreased renal function, respiratory disorders, uncontrolled peptic ulcer disease.
Taking any other medications, including over the counter supplements with the exception of oral contraceptives for women
Pregnancy. Females of child-bearing age must be using an effective contraceptive method.
History of smoking, substance abuse or dependence.
Contraindication to MR scan (claustrophobia, cardiac pacemakers, metal clips and stents on blood vessels, artificial heart valves, artificial arms, hands, legs, etc., brain stimulator devices, implanted drug pumps, ear implants, eye implants or known metal fragments in eyes, exposure to shrapnel or metal filings, other metallic surgical hardware in vital areas, certain tattoos with metallic ink, certain transdermal patches, metal- containing intrauterine devices)
Medical condition that would prevent blood draws, including current anti-coagulant or anti-aggregant therapy, tendency for abnormal scarring (e.g. keloids).
Difficulty in swallowing capsules.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Nicotinamide riboside 2g/day	Nicotinamide Riboside	Participants will receive NR at a dose of 2g/day

Primary Outcome Measures

Name	Time	Method
Change From Baseline to the End of Treatment in Brain NAD+/NADH Ratio	Baseline and after 15 days of supplement use	Change from baseline to the end of treatment in brain NAD+/NADH ratio as measured by in vivo 31P magnetic resonance spectroscopy The NAD+/NADH ratio is calculated by first quantifying NAD+ and NADH separately in the data and then obtaining a simple ratio. There is a normative NAD+/NADH ratio range in healthy brain and deviations from this level in either direction can be a sign of pathology.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline to the End of Treatment in Brain Phosphocreatine (PCr) to Adenosine Triphosphate (ATP) Ratio (PCr/ATP)	Baseline and after 15 days of supplement use	Change from baseline to the end of treatment in brain phosphocreatine (PCr) to adenosine triphosphate (ATP) ratio (PCr/ATP) as measured by in vivo 31P magnetic resonance spectroscopy
Change From Baseline to the End of Treatment in Brain Creatine Kinase (CK) Enzyme Rate	Baseline and after 15 days of supplement use	Change from baseline to the end of treatment in creatine kinase (CK) enzyme rate as measured by in vivo 31P magnetic resonance spectroscopy
Change From Baseline to the End of Treatment in Muscle Phosphocreatine (PCr) to Adenosine Triphosphate (ATP) Ratio (PCr/ATP)	Baseline and after 15 days of supplement use	Change from baseline to the end of treatment in calf muscle phosphocreatine (PCr) to adenosine triphosphate (ATP) ratio (PCr/ATP) as measured by in vivo 31P magnetic resonance spectroscopy
Change From Baseline to the End of Treatment in Muscle Creatine Kinase (CK) Enzyme Rate	Baseline and after 15 days of supplement use	Change from baseline to the end of treatment in calf muscle creatine kinase (CK) enzyme rate as measured by in vivo 31P magnetic resonance spectroscopy
Change From Baseline to the End of Treatment in Muscle NAD+/NADH Ratio	Baseline and after 15 days of supplement use	Change from baseline to the end of treatment in calf muscle NAD+/NADH ratio as measured by in vivo 31P magnetic resonance spectroscopy