Trial Outcomes & Findings for Nicotinamide Riboside on Mitochondrial Function in Li-Fraumeni Syndrome (NCT NCT03789175)

NCT ID: NCT03789175

Last Updated: 2020-12-08

Results Overview

The effect of nicotinamide riboside (NR) supplementation on the phosphocreatine (PCr) recovery time constant (Tc) of skeletal muscle after exercise as a marker of mitochondrial oxidative phosphorylation capacity. The phosphocreatine level will be measured using 31P-magnetic resonance spectroscopy (MRS) during the following sequence of 3-minute rest, 2-minute exercise, and 6-minute recovery periods. The 31P spectra will be obtained during these periods and analyzed with the use of SAGE 7 (GE Healthcare) and IDL, version 6.4 (Exelis Visual Information Solutions), software. The single exponential recovery time constant (Tc) is calculated from the post-exercise recovery period data.

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 1 participants
• Primary outcome timeframe: Baseline to 12 weeks
• Results posted on: 2020-12-08

Participant Flow

This is a one-subject study so there are no recruitment or screening of other subjects.

Participant milestones

Measure	Nicotinamide Riboside (NR) in Li-Fraumeni Syndrome Nicotinamide riboside (NR) to be initiated at week 0 at dose of 250 mg twice a day. At Week 1, NR will be titrated to 500 mg twice a day. At Week 6, NR will be titrated to 750 mg twice a day. At Week 7, NR will be titrated to 1000 mg twice a day or as tolerated until end of week 12. At week 12, if participant responds to primary endpoint, participant will washout of NR at week 18 then restart NR at week 24 until week 30. If there is not response to NR treatment at week 12, the participant may continue taking NR at a tolerated dose until week 24 and the primary endpoint will be re-measured. If participant has a positive response to NR treatment at week 24, then the participant will washout of NR until week 30, at which time the primary endpoint will be re-measured to ensure return to baseline. If there is no response to continued NR treatment at week 24, the study will be ended.
Week 0 to Week 12 of NR STARTED	1
Week 0 to Week 12 of NR COMPLETED	1
Week 0 to Week 12 of NR NOT COMPLETED	0
Week 12 to Week 24 of NR STARTED	1
Week 12 to Week 24 of NR COMPLETED	1
Week 12 to Week 24 of NR NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Nicotinamide Riboside on Mitochondrial Function in Li-Fraumeni Syndrome

Baseline characteristics by cohort

Measure	Nicotinamide Riboside (NR) in Li-Fraumeni Syndrome n=1 Participants Nicotinamide riboside (NR) to be initiated at week 0 at dose of 250 mg twice a day. At Week 1, NR will be titrated to 500 mg twice a day. At Week 6, NR will be titrated to 750 mg twice a day. At Week 7, NR will be titrated to 1000 mg twice a day or as tolerated until end of week 12. At week 12, if participant responds to primary endpoint, participant will washout of NR at week 18 then restart NR at week 24 until week 30. If there is not response to NR treatment at week 12, the participant may continue taking NR at a tolerated dose until week 24 and the primary endpoint will be re-measured. If participant has a positive response to NR treatment at week 24, then the participant will washout of NR until week 30, at which time the primary endpoint will be re-measured to ensure return to baseline. If there is no response to continued NR treatment at week 24, the study will be ended.
Age, Continuous	40 years STANDARD_DEVIATION 0 • n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	1 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to 12 weeks

The effect of nicotinamide riboside (NR) supplementation on the phosphocreatine (PCr) recovery time constant (Tc) of skeletal muscle after exercise as a marker of mitochondrial oxidative phosphorylation capacity.

The phosphocreatine level will be measured using 31P-magnetic resonance spectroscopy (MRS) during the following sequence of 3-minute rest, 2-minute exercise, and 6-minute recovery periods. The 31P spectra will be obtained during these periods and analyzed with the use of SAGE 7 (GE Healthcare) and IDL, version 6.4 (Exelis Visual Information Solutions), software. The single exponential recovery time constant (Tc) is calculated from the post-exercise recovery period data.

Outcome measures

Measure	Baseline Phosphocreatine (PCr) Recovery Tc Measurement n=1 Participants All participants prior to initiation of nicotinamide riboside (NR).	Nicotinamide Riboside (NR) in Li-Fraumeni Syndrome n=1 Participants Nicotinamide riboside (NR) to be initiated at week 0 at dose of 250 mg twice a day. At Week 1, NR will be titrated to 500 mg twice a day. At Week 6, NR will be titrated to 750 mg twice a day. At Week 7, NR will be titrated to 1000 mg twice a day or as tolerated until end of week 12. At week 12, if participant responds to primary endpoint, participant will washout of NR at week 18 then restart NR at week 24 until week 30. If there is not response to NR treatment at week 12, the participant may continue taking NR at a tolerated dose until week 24 and the primary endpoint will be re-measured. If participant has a positive response to NR treatment at week 24, then the participant will washout of NR until week 30, at which time the primary endpoint will be re-measured to ensure return to baseline. If there is no response to continued NR treatment at week 24, the study will be ended.
Change in PCr Recovery Tc Measurement From Baseline to 12 Week NR Supplementation Using the 31P-MRS Skeletal Muscle Submaximal Exercise.	60 Seconds	73 Seconds

SECONDARY outcome

Timeframe: Baseline to 12 weeks

Measure change in time of cardiopulmonary exercise test (CPET) to determine exercise tolerance from baseline to 12 weeks of NR supplementation.

Outcome measures

Measure	Baseline Phosphocreatine (PCr) Recovery Tc Measurement n=1 Participants All participants prior to initiation of nicotinamide riboside (NR).	Nicotinamide Riboside (NR) in Li-Fraumeni Syndrome n=1 Participants Nicotinamide riboside (NR) to be initiated at week 0 at dose of 250 mg twice a day. At Week 1, NR will be titrated to 500 mg twice a day. At Week 6, NR will be titrated to 750 mg twice a day. At Week 7, NR will be titrated to 1000 mg twice a day or as tolerated until end of week 12. At week 12, if participant responds to primary endpoint, participant will washout of NR at week 18 then restart NR at week 24 until week 30. If there is not response to NR treatment at week 12, the participant may continue taking NR at a tolerated dose until week 24 and the primary endpoint will be re-measured. If participant has a positive response to NR treatment at week 24, then the participant will washout of NR until week 30, at which time the primary endpoint will be re-measured to ensure return to baseline. If there is no response to continued NR treatment at week 24, the study will be ended.
Change in Time of CPET Time as a Measure of Exercise Tolerance From Baseline to 12 Weeks of NR Supplementation.	12.1 Minutes	11.68 Minutes

Adverse Events

Nicotinamide Riboside (NR) in Li-Fraumeni Syndrome

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Nicotinamide Riboside (NR) in Li-Fraumeni Syndrome n=1 participants at risk Nicotinamide riboside (NR) to be initiated at week 0 at dose of 250 mg twice a day. At Week 1, NR will be titrated to 500 mg twice a day. At Week 6, NR will be titrated to 750 mg twice a day. At Week 7, NR will be titrated to 1000 mg twice a day or as tolerated until end of week 12. At week 12, if participant responds to primary endpoint, participant will washout of NR at week 18 then restart NR at week 24 until week 30. If there is not response to NR treatment at week 12, the participant may continue taking NR at a tolerated dose until week 24 and the primary endpoint will be re-measured. If participant has a positive response to NR treatment at week 24, then the participant will washout of NR until week 30, at which time the primary endpoint will be re-measured to ensure return to baseline. If there is no response to continued NR treatment at week 24, the study will be ended.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	100.0% 1/1 • Number of events 1 • 24 weeks
Metabolism and nutrition disorders Muscle cramp	100.0% 1/1 • Number of events 1 • 24 weeks
Musculoskeletal and connective tissue disorders Muscle Tightness	100.0% 1/1 • Number of events 1 • 24 weeks

Additional Information

Dr. Paul Hwang

NHLBI, NIH

Phone: 3014353068

Email: hwangp@mail.nih.gov

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place