NADMet: Nicotinamide Adenine Dinucleotide and Skeletal Muscle Metabolic Phenotype

Sponsor

University of Birmingham (Other)

Overall Status

Unknown status

CT.gov ID

NCT02950441

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study is designed to assess the physiological consequences of elevating Nicotinamide Adenine Dinucleotide (NAD+) availability using Nicotinamide Riboside (NR) supplementation in skeletal muscle tissue, and examine its effect upon muscle metabolic phenotype.

Condition or Disease	Intervention/Treatment	Phase
Aging	Dietary Supplement: Nicotinamide Riboside Other: Placebo	Phase 2

Detailed Description

-NAD+ sensitive metabolic decline in ageing, including sarcopenia, leads to a reduction in energy metabolism, contribute to chronic inflammation, disposing individuals to metabolic disease and overall decreased later-life health. Prominent metabolic changes include a decline in NAD+ content and deterioration in muscle NAD+ mediated signalling and mitochondrial function, ultimately compromising skeletal muscle and whole body energy homeostasis.

The most efficient means to boost NAD+ in muscle appears to be oral delivery of NR, and participants will be supplemented with 1000mg NR (2x x250mg tablets twice daily) for 3 weeks.

Hypothesis: elevating skeletal muscle NAD+ bioavailability using NR supplementation will increase markers of mitochondrial function and that will manifest as a more favourable metabolic profile.
Study Setting: the study will be carried out at the NIHR/Wellcome Trust Clinical Research Facility, Queen Elizabeth Hospital Birmingham.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

12 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Nicotinamide Adenine Dinucleotide and Skeletal Muscle Metabolic Phenotype (NADMet)

Study Start Date :

Jun 1, 2016

Anticipated Primary Completion Date :

Sep 1, 2018

Anticipated Study Completion Date :

Sep 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Nicotinamide Riboside 1000mg (2x250mg tablets twice daily)	Dietary Supplement: Nicotinamide Riboside
Placebo Comparator: Placebo Two tablets twice daily	Other: Placebo

Arm

Intervention/Treatment

Experimental: Nicotinamide Riboside

1000mg (2x250mg tablets twice daily)

Dietary Supplement: Nicotinamide Riboside

Placebo Comparator: Placebo

Two tablets twice daily

Other: Placebo

Outcome Measures

Primary Outcome Measures

Mitochondrial function assessment in skeletal muscle using high resolution respirometry [Following 3 weeks of NR supplementation]
Mitochondrial function assessment on muscle biopsies using high resolution respirometry
Skeletal muscle NAD+ levels in vastus lateralis biopsy using targeted metabolomics [Following 3 weeks of NR supplementation]

Secondary Outcome Measures

Improvement in response to oral glucose tolerance test/HOMA-IR [Following 3 weeks of NR supplementation]
Improvement in lipid profile [Following 3 weeks of NR supplementation]
Muscle Arterio-Venous Difference - Tissue-specific metabolite trafficking, oxygen consumption and CO2 production [Following 3 weeks of NR supplementation]
Muscle biopsy: adaptive expression profile (genomic) [Following 3 weeks of NR supplementation]
Changes in resting metabolic rate using indirect calorimetry [Following 3 weeks of NR supplementation]
24 hour urine collection - NAD+ metabolomics and changes in steroid ratios using Gas chromatography/ mass spectrometry [Following 3 weeks of NR supplementation]
Muscle strength - grip testing [Following 3 weeks of NR supplementation]

Eligibility Criteria

Criteria

Ages Eligible for Study:

70 Years to 80 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Male sex
Age 70-80 years
BMI 20-30kg/m2
Participants who are able to discontinue aspirin for 3 days prior to the muscle biopsy
Participants who are able to discontinue statins and vitamin D supplements for a week before the second visit and for the duration of the study

Exclusion Criteria:

Serious active medical conditions including inflammatory diseases or malignancies
Significant past medical history including diabetes mellitus, ischaemic heart disease, cerebrovascular disease, significant respiratory disease requiring medication, epilepsy
High blood pressure (BP>160/100mmHg)
Oral Anticoagulants (like Warfarin, Dabigatran, Rivaroxaban) or Clopidogrel therapy which will increase the risk of bruising following a muscle biopsy