Nicotinamide Adenine Dinucleotide and Skeletal Muscle Metabolic Phenotype (NADMet)
试验速览
- 阶段
- 2 期
- 入组人数
- 12
- 试验地点
- 2
- 主要终点
- Skeletal muscle NAD+ levels in vastus lateralis biopsy using targeted metabolomics
研究概览
简要总结
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.
详细描述
-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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 70 Years 至 80 Years（Older Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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
结局指标
主要结局
Skeletal muscle NAD+ levels in vastus lateralis biopsy using targeted metabolomics
时间窗: Following 3 weeks of NR supplementation
Mitochondrial function assessment in skeletal muscle using high resolution respirometry
时间窗: Following 3 weeks of NR supplementation
Mitochondrial function assessment on muscle biopsies using high resolution respirometry
次要结局
- Improvement in lipid profile(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)
- Improvement in response to oral glucose tolerance test/HOMA-IR(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)
- Changes in resting metabolic rate using indirect calorimetry(Following 3 weeks of NR supplementation)
- Muscle strength - grip testing(Following 3 weeks of NR supplementation)
- Muscle biopsy: adaptive expression profile (genomic)(Following 3 weeks of NR supplementation)