Nicotinamide Adenine Dinucleotide and Skeletal Muscle Metabolic Phenotype

Aging Clinical Trial

— NADMet  

Official title:

Nicotinamide Adenine Dinucleotide and Skeletal Muscle Metabolic Phenotype (NADMet)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02950441
• Other study ID #: RG_15-152
• Status: Recruiting
• Phase: Phase 2
• First received: October 25, 2016
• Last updated: June 5, 2017
• Start date: June 2016
• Est. completion date: September 2019

Study information

• Verified date: October 2016
• Source: University of Birmingham
• Contact: Yasir Elhassan, MRCP
• Phone: +441214158705
• Email: y.mohamedelhassan[@]bham.ac.uk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 12
• Est. completion date: September 2019
• Est. primary completion date: September 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 70 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Aging

Intervention

Dietary Supplement:
• Nicotinamide Riboside

Other:
• Placebo

Locations

Country	Name	City	State
United Kingdom	University Hospitals Birmingham NHS Foundation Trust	Birmingham	West Midlands

Sponsors (1)

Lead Sponsor	Collaborator
University of Birmingham

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Skeletal muscle NAD+ levels in vastus lateralis biopsy using targeted metabolomics		Following 3 weeks of NR supplementation
Secondary	Improvement in response to oral glucose tolerance test/HOMA-IR		Following 3 weeks of NR supplementation
Secondary	Improvement in lipid profile		Following 3 weeks of NR supplementation
Secondary	Muscle Arterio-Venous Difference - Tissue-specific metabolite trafficking, oxygen consumption and CO2 production		Following 3 weeks of NR supplementation
Secondary	Muscle biopsy: adaptive expression profile (genomic)		Following 3 weeks of NR supplementation
Secondary	Changes in resting metabolic rate using indirect calorimetry		Following 3 weeks of NR supplementation
Secondary	24 hour urine collection - NAD+ metabolomics and changes in steroid ratios using Gas chromatography/ mass spectrometry		Following 3 weeks of NR supplementation
Secondary	Muscle strength - grip testing		Following 3 weeks of NR supplementation