The main of objective of this study is to determine whether supplementation of NAD+-precursors can stimulate skeletal muscle mitochondrial function in physically compromised, elderly humans. Secondary objectives are the determination of 1) blood and…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
veroudering, energiemetabolisme.
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main outcome parameters relate to the anticipated differences in
mitochondrial function and include ex vivo mitochondrial respiratory capacity,
in vivo mitochondtrial capacity, resting- and exercising energy metabolism, and
in vivo mitochondrial capacity.
Secondary outcome
- Glucose tolerance;
- Physical performance;
- Intramuscular cellular lipid content;
- Hepatic fat;
- Physical activity;
- Quality of life;
- Markers of mitochondrial metabolism.
- Blood metabolites and biomarkers.
Background summary
One of the most striking features of the aging process is the progressive loss
of muscle mass (sarcopenia) and physical function. The loss in skeletal muscle
mass and tissue function, leads to mobility impairment, increased risk of
falls, physical frailty but also metabolic impairments. Compromised physical
function increases the risk of dependence in activities of daily living and
care need. Interestingly, it was previously shown in mice, that aging is
associated with reduced intracellular NAD+ levels in skeletal muscle. It is now
generally accepted that NAD+ metabolism is a main pathway in the regulation of
mitochondrial function in skeletal muscle and would be a target for
intervention to stimulate mitochondrial function and thereby prevent
age-related decline in muscle physical function. To this end, this study aims
to determine whether supplementing with the NAD+-precursors NA, NAM and
tryptophan can stimulate skeletal muscle mitochondrial function in physically
compromised, elderly humans.
Study objective
The main of objective of this study is to determine whether supplementation of
NAD+-precursors can stimulate skeletal muscle mitochondrial function in
physically compromised, elderly humans. Secondary objectives are the
determination of 1) blood and skeletal muscle NAD+ levels, 2) body composition,
3) molecular pathways and gene transcription responsible for improved
mitochondrial health and function, 4) physical function and -activity, and 5)
glucose tolerance upon NAD+-precursor supplementation.
Study design
A double-blind, randomised, controlled, cross-over intervention trial, in which
NAD+-precursor supplementation will be compared to control.
Intervention
The subjects will receive at random the following products: 1) intervention
product containing the NAD+-precursors nicotinic acid, nicotinamide, and
tryptophan in a whey protein source; 2) control product consisting of an amino
acid mix resembling the whey protein source devoid of tryptophan, nicotinic
acid and nicotinamide.
Study burden and risks
This study will lead to novel insights with respect to the ability of food
constituents to improve mitochondrial function and health in the physically
compromised elderly population. However, this study is not expected to be
directly beneficial to the participants. The major burden to the subjects is a
large time investment. Subjects will be asked to attend the university on, in
total, 12 occasions for measurement procedures. Additionally, subjects will be
asked to consume a nutritional product containing NAD+-precursors versus a
control on a daily basis for a period of 32 days each. The experimental
procedures are without risks, except for blood sampling and sampling of muscle
biopsies, which can occasionally cause a local hematoma or bruising. The risk
of infection or prolonged bleeding is low due to state of the art techniques
and sterility measures. The maximal exercise test and cycling protocol can
cause muscle soreness. Measurements performed during the time course of the
study can potentially lead to coincidental medical findings. Subjects will be
informed about such a finding and possibly be advised to contact a doctor about
this.
Universiteitssingel 50
Maastricht 6200 MD
NL
Universiteitssingel 50
Maastricht 6200 MD
NL
Listed location countries
Age
Inclusion criteria
- Males and females
- Age * 65 * 80 years;
- BMI * 20 kg/m2 * 30 kg/m2;
- Normal physical activity levels: maximum of 1 hour per week engagement in a structured exercise session;
- 6-minute walking distance of 465 meters or less;
- Subject should be in sufficient health to participate in the experiments, to be judged by the responsible physician based on the subject's medical history.
Exclusion criteria
- Not meeting all inclusion criteria;
- Smoking;
- Excessive alcohol use and/or drug abuse;
- Subjects with diabetes mellitus type 2;
- Significant food allergies or intolerances concerning the study products;
- Participation in another biomedical study within 1 month before the first study visit, possibly interfering with the study results;
- Medication use known to hamper subject*s safety during the study procedures;
- Subjects who use selective serotonin re-uptake inhibitors (SSRI), or selective norepinephrin re-uptake inhibitors (SNRI), or monoamino oxidase inhibitors (MAO-inhibitors), or clomipramine, or St. John*s wort (Hypericum perforatum);
- Subjects with contra-indications for MRI;
- Subjects who do not want to be informed about unexpected medical findings;
- Subjects who do not want that their treating physician to be informed;
- Co-morbidities to which the intervention or program the may pose as a complicating factor;
- Inability to participate and/or complete the required measurements.
Design
Recruitment
Followed up by the following (possibly more current) registration
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Other (possibly less up-to-date) registrations in this register
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In other registers
| Register | ID |
|---|---|
| CCMO | NL61204.068.17 |