Assessing the Safety and Tolerability of NMN in DHDDS-CDG

Small Cohort, Off Label Treatment Assessing the Safety and Tolerability of NMN in DHDDS-Congenital Disorder of Glycosylation (DHDDS-CDG)

The primary objective of this study is to evaluate the safety and tolerability of the dietary supplement, nicotinamide mononucleotide (NMN), in individuals with dehydrodolichol diphosphate synthase congenital disorder of glycosylation (DHDDS-CDG). This will to contribute to knowledge that will allow healthcare providers to make informed decisions about recommending this dietary supplement in this population.

This is a small cohort, off label treatment study assessing the safety, and tolerability of the over-the-counter supplement, nicotinamide mononucleotide (NMN) in individuals with heterozygous DHDDS-CDG. There is no treatment currently available for this progressive disease and there is evidence that this supplement may be a viable supportive therapy. This study will assess the safety and tolerability of this supplement, as well as examine NMN's effect on clinical manifestations of DHDDS-CDG, including gait abnormalities and hand tremor. This phase 1, open-label study will have a 4 week run-in period, a treatment period of 6 months during which the participants will take 250 mg NMN daily, and an optional extension period of 6 more months. Study assessments will involve physician assessments, lab tests, physical exams, vital signs, height/weight measurements, participant goal-setting, and tests to assess gait performance and hand tremor.

Inclusion Criteria:

• Subject is ≥ 4 years old
• Subject has biologically and genetically proven heterozygous DHDDS-CDG.
• Subject/legally authorized representative (LAR) is able to understand and provide written informed consent, and assent (as applicable) to participate in this study.

Exclusion Criteria:

• Subject has intellectual disability with IQ<52 (moderate or lower IQ intellectual disability).

• In the site Principal Investigator's opinion, subject has a history of intolerance to NMN or other niacin metabolite supplement that precludes the subject from participation in this study.

• Subject has any of the following:

  • Liver failure
  • ALT level >5x ULN
  • AST level >5x ULN
  • eGFR < 30 OR creatinine >180 mmol/L

• Subject is pregnant.

• Use of investigational compounds within the previous 6 months or current enrollment in another trial involving investigational compounds.

• Concomitant use of the following medications that could interact with orally administered NMN:

  • Aspirin
  • Metformin
  • Statins or other cholesterol-lowering drugs

• In the site Principal Investigator's opinion, subject is not able or willing to comply with the trial requirements.