Nicotinamide Riboside on Mitochondrial Function in Li-Fraumeni Syndrome

What Was Tested

This registered phase 1, phase 2 trial tested NAD+.

Background: Nicotinamide riboside (NR) is a vitamin B3 dietary supplement.

Researchers want to study how skeletal muscle responds to NR in an individual who has Li-Fraumeni Syndrome and slow muscle energy recovery after exercise.

It had 1 arm (groups): Nicotinamide riboside (NR) in Li-Fraumeni syndrome (other).

The registry classes the interventions as dietary supplement.

More on the Plan

The researchers have previously reported that inherited mutations of TP53, which causes the premature cancer disorder Li-Fraumeni syndrome (LFS), can promote mitochondrial function both in patients and mouse models.

In the course of their follow up studies, the researchers encountered a LFS patient with a long-standing history of fatigue and muscle weakness of unclear etiology.

Remarkably, the researchers observed that culturing the LFS patients fibroblasts in medium containing NR rescued the severe deficit in mitochondrial respiration.

While continuing their investigations into the molecular mechanism(s) underlying the mitochondrial dysfunction observed in this patient, the in vitro rescue of the respiratory deficiency by NR presents a unique opportunity to investigate whether it can also be observed in vivo using skeletal muscle 31P-MRS.

Who Took Part

The registry lists 1 actual participants took part.

It was open to people of any sex aged from 18 years up to 70 years.

Healthy volunteers were not accepted; participants needed the condition being studied.

Examples of who could join: At least 18-years of age and able to give informed consent. Have delayed phosphocreatine (PCr) recovery time constant \>45 sec by 31P-magnetic resonance spectroscopy (MRS) testing and a history of fatigue symptoms. Have Li-Fraumeni syndrome and confirmed TP53 mutation by genetic testing. Committed to using reliable contraception which may include abstinence during study participation. Female participants of child-bearing ability and potential willing to commit to reliable contraception while participating in the study.

The full record lists 7 inclusion and 5 exclusion criteria; among the exclusions: current systemic treatment for cancer; unable to perform required study visits or procedures; magnetic resonance imaging (mri) incompatible hardware.

How the Study Was Run

The set-up was single-group and open-label.

Nothing was hidden in this open-label NAD+ study: the participants and staff both knew the treatment.

Everyone received the same intervention, so there was no separate comparison group inside the trial.

It started in 2019-03-25 with completion listed for 2019-11-01.

It ran at 1 site in United States.

Its stated primary purpose is basic science.

What Was Measured

Researchers chose this as the main measure: Change in PCr Recovery Tc Measurement From Baseline to 12 Week NR Supplementation Using the 31P-MRS Skeletal Muscle Submaximal Exercise (time frame: Baseline to 12 weeks).

It also tracked 1 secondary outcome, for example Change in Time of CPET Time as a Measure of Exercise Tolerance From Baseline to 12 Weeks of NR Supplementation.

What This Means in Plain Language

Put simply, this is a phase 1, phase 2 trial of NAD+ in 1 people.

Its size is small, so on its own it can only give an early look.

The trial is marked completed; results are posted on the registry, and this page does not restate them.

More context: the NAD+ compound page, all human trials.