Nicotinamide Adenine Dinucleotide and Skeletal Muscle Metabolic Phenotype (NADMet)

Nicotinamide Adenine Dinucleotide and Skeletal Muscle Metabolic Phenotype (NADMet)

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.

Study Overview

• Status: Unknown
• Conditions: Aging
• Intervention / Treatment: Other: Placebo; Dietary supplement: Nicotinamide Riboside

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 Type: Interventional
• Enrollment (Anticipated): 12
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • West Midlands
    • Birmingham, West Midlands, United Kingdom, B15 2TH
      • Recruiting
      • University Hospitals Birmingham NHS Foundation Trust
      • Contact: Yasir Elhassan, MRCP; Phone Number: +441214158705; Email: y.mohamedelhassan@bham.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 70 years to 80 years (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mitochondrial function assessment in skeletal muscle using high resolution respirometry	Mitochondrial function assessment on muscle biopsies using high resolution respirometry	Following 3 weeks of NR supplementation
Skeletal muscle NAD+ levels in vastus lateralis biopsy using targeted metabolomics		Following 3 weeks of NR supplementation

Secondary Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: University of Birmingham
• Investigators: Principal Investigator: Gareth Lavery, PhD, Institute of Metabolism and Systems Research, University of Birmingham

Study record dates

Study Major Dates

• Study Start: June 1, 2016
• Primary Completion (Anticipated): September 1, 2018
• Study Completion (Anticipated): September 1, 2019

Study Registration Dates

• First Submitted: October 25, 2016
• First Submitted That Met QC Criteria: October 27, 2016
• First Posted (Estimate): November 1, 2016

Study Record Updates

• Last Update Posted (Actual): June 7, 2017
• Last Update Submitted That Met QC Criteria: June 5, 2017
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: Nicotinamide Riboside; Metabolism; Skeletal muscle; Nicotinamide Adenine Dinucleotide
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Antimetabolites; Micronutrients; Hypolipidemic Agents; Lipid Regulating Agents; Vitamins; Vitamin B Complex; Nicotinic Acids; Niacinamide; Niacin
• Other Study ID Numbers: RG_15-152

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No