NAD+ Precursor Supplementation in Friedreich's Ataxia

Friedreich Ataxia Clinical Trial

Official title:

A Phase 2a Study of NAD+ Precursor Supplementation in Friedreich's Ataxia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04817111
• Other study ID #: 19-016525
• Secondary ID: MIB-626-201
• Status: Completed
• Phase: Phase 2
• Start date: May 17, 2021
• Est. completion date: May 19, 2022

Study information

• Verified date: July 2023
• Source: Metro International Biotech, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective is to test the safety and tolerability of short-term therapy with a nicotinamide adenine dinucleotide (NAD+) precursor (MIB-626) in adults with Friedreich's Ataxia (FA) without overt heart failure and with a left ventricular ejection fraction ≥ 40%. A key secondary objective is to test the effects of MIB-626 on cardiac and skeletal muscle bioenergetics.

Description:

The primary focus for this protocol is safety and tolerability. We will systematically assess for adverse events using a safety monitoring uniform report form. We will also use cardiac 31-Phosphorus-Magnetic Resonance Spectroscopy (MRS) to measure the Phosphocreatine(PCr)/Adenosine triphosphate (ATP)- γ ratio before and after treatment with MIB-626. In addition, if time permits we will use proton (1H)-MRS to measure skeletal muscle nicotinamide adenine dinucleotide (NAD+) before and after treatment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 7
• Est. completion date: May 19, 2022
• Est. primary completion date: May 19, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 64 Years

Eligibility

Inclusion Criteria:

• Molecular diagnosis of Friedreich's Ataxia (FA).
• Males and females, ages 18 years to < 65 years.

Exclusion Criteria:

• Known sensitivity to nicotinamide-containing compounds.
• Concurrent use of Vitamin B3 supplements and/or any medications likely to increase risk of MIB-626 toxicity.
• HgbA1c > (great than or equal to) 8.5% and or Diabetes Mellitus (DM) requiring insulin or insulin secretagogue.
• Kidney disease (Estimated Glomerular Filtration Rate (eGFR) < 60 ml/min/1.73 m2) using serum creatinine and MDRD equation. The eGFR levels will be calculated using the Modified Diet in Renal Disease Study (MDRD) equation, which is the equation used by the Children's Hospital Of Philadelphia laboratory.
• Liver disease (Aspartate Aminotransferase (AST)/Alanine Aminotransferase (ALT) > 3 x Upper Limit of Normal)
• Severe co-existing cardiac disease (Ejection Fraction (EF) < 40%, known arrhythmia) as demonstrated by an echocardiogram within 12 months of screening.
• Any contraindication to MRI, including spinal rods (related to unknown safety considerations for cardiac 31-Phosphorus -MRS).
• Use of any investigational agent within 4 weeks of enrollment.
• Females: Pregnant/lactating or planning to become pregnant during their participation.
• Any medical condition that, in the opinion of the investigator, will interfere with the safe completion of the study.

Related Conditions & MeSH terms

• Ataxia
• Cerebellar Ataxia
• Friedreich Ataxia

Intervention

Drug:
• MIB-626
Two (2) 500 mg Tablets, By Mouth, Daily

Locations

Country	Name	City	State
United States	The Children's Hospital of Philadelphia	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Metro International Biotech, LLC	Children's Hospital of Philadelphia

Country where clinical trial is conducted

United States, 

References & Publications (3)

Bagga P, Wilson N., DeBrosse D., Hariharan H., Reddy R., editor. In vivo detection of NAD+ in human calf muscle at 7T using 28-channel knee volume coil. International Society for Magnetic Resonance in Medicine; 2019; Montreal, Canada.

DeBrosse C, Nanga RPR, Wilson N, D'Aquilla K, Elliott M, Hariharan H, Yan F, Wade K, Nguyen S, Worsley D, Parris-Skeete C, McCormick E, Xiao R, Cunningham ZZ, Fishbein L, Nathanson KL, Lynch DR, Stallings VA, Yudkoff M, Falk MJ, Reddy R, McCormack SE. Muscle oxidative phosphorylation quantitation using creatine chemical exchange saturation transfer (CrCEST) MRI in mitochondrial disorders. JCI Insight. 2016 Nov 3;1(18):e88207. doi: 10.1172/jci.insight.88207. — View Citation

Patel M, Isaacs CJ, Seyer L, Brigatti K, Gelbard S, Strawser C, Foerster D, Shinnick J, Schadt K, Yiu EM, Delatycki MB, Perlman S, Wilmot GR, Zesiewicz T, Mathews K, Gomez CM, Yoon G, Subramony SH, Brocht A, Farmer J, Lynch DR. Progression of Friedreich ataxia: quantitative characterization over 5 years. Ann Clin Transl Neurol. 2016 Jul 25;3(9):684-94. doi: 10.1002/acn3.332. eCollection 2016 Sep. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Individuals With Treatment-emergent Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 5.0.	Safety will be monitored through collection of laboratory assessments (CBC, complete metabolic profile, lipid profile, HbA1c), vital signs (heart rate, blood pressure), and ECG, all of which will be reviewed for clinically relevant abnormalities, and standardized assessment of symptoms. We report the proportion of individuals who had at least one treatment-emergent adverse event of Grade 1 or higher.	14 Days
Secondary	Cardiac 31-Phosphorus-Magnetic Resonance Spectroscopy (MRS): Phosphocreatine (PCr)/Adenosine Tri-Phosphate (ATP) Ratio	Measure the within-participant change in PCr/ATP ratio before and after treatment with MIB-626.	Change from baseline to 14 days.
Secondary	Post-Exercise Creatine Chemical Exchange Saturation Transfer (CrCEST) Magnetic Resonance Imaging (MRI)	Assess the within-participant change in skeletal muscle post-exercise CrCEST recovery (an index of skeletal muscle mitochondrial oxidative phosphorylation capacity).	Change from baseline to 14 days.
Secondary	Grip Strength	Assess within-participant changes in grip strength (via hand grip dynamometry) before and after treatment with MIB-626.	Change from baseline to 14 days.
Secondary	Concentration of Nicotinamide Adenine Dinucleotide (NAD+) in Whole Blood	Measure the concentration of NAD+ in whole blood before and after treatment with MIB-626.	Change from baseline to 14 days.