Clinical trial NCT02950441: Nicotinamide Adenine Dinucleotide and Skeletal Muscle Metabolic Phenotype
Official title: Nicotinamide Adenine Dinucleotide and Skeletal Muscle Metabolic Phenotype (NADMet)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Aging
Keywords: Nicotinamide Riboside
Nicotinamide Adenine Dinucleotide
Skeletal muscle
Metabolism
Lead sponsor: University of Birmingham
Sponsor class: OTHER
First posted: 2016-11-01
Enrollment: 12
Sex: MALE
Minimum age (years): 70
Maximum age (years): 80
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Mitochondrial function assessment in skeletal muscle using high resolution respirometry
timeFrame: Following 3 weeks of NR supplementation
measure: Skeletal muscle NAD+ levels in vastus lateralis biopsy using targeted metabolomics
timeFrame: Following 3 weeks of NR supplementation
Secondary outcomes:
measure: Improvement in response to oral glucose tolerance test/HOMA-IR
timeFrame: Following 3 weeks of NR supplementation
measure: Improvement in lipid profile
timeFrame: Following 3 weeks of NR supplementation
measure: Muscle Arterio-Venous Difference - Tissue-specific metabolite trafficking, oxygen consumption and CO2 production
timeFrame: Following 3 weeks of NR supplementation
measure: Muscle biopsy: adaptive expression profile (genomic)
timeFrame: Following 3 weeks of NR supplementation
measure: Changes in resting metabolic rate using indirect calorimetry
timeFrame: Following 3 weeks of NR supplementation
measure: 24 hour urine collection - NAD+ metabolomics and changes in steroid ratios using Gas chromatography/ mass spectrometry
timeFrame: Following 3 weeks of NR supplementation
measure: Muscle strength - grip testing
timeFrame: Following 3 weeks of NR supplementation
Other outcomes:
Locations:
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham NHS Foundation Trust
state: West Midlands
Study officials:
affiliation: Institute of Metabolism and Systems Research, University of Birmingham
name: Gareth Lavery, PhD
role: PRINCIPAL_INVESTIGATOR
References: