Effects of Vitamin B3 in Patients With Ataxia Telangiectasia

Effects of Nicotinamide Riboside (Vitamin B3) in Patients With Ataxia Telangiectasia.

This clinical trial investigates the effects of nicotinamide riboside (vitamin B3) on the disease course of patients with ataxia telangiectasia.

Patients will be treated during four consecutive months with nicotinamide riboside (25mg/kg/day), followed by a washout period of two months.

Main study parameters/endpoints: Ataxia, dysarthria, quality of life, laboratory parameters.

Study Overview

• Status: Completed
• Conditions: Ataxia Telangiectasia; ATM Gene Mutation
• Intervention / Treatment: Dietary supplement: Vitamin B3

Detailed Description

Rationale: Ataxia Telangiectasia (A-T) is an autosomal recessively inherited neurodegenerative disorder, with a high cancer risk, that also affects the immune and respiratory system. Therapy for A-T is restricted to symptomatic treatment including rehabilitation care, combined with infection prevention and treatment, and screening for pulmonary dysfunction and malignancies. A-T is caused by mutations in the ATM gene. The ATM protein plays a pivotal role in more than 100 different biochemical processes, among which cellular energy metabolism, cell signaling, and DNA repair. Nicotinamide adenine dinucleotide (NAD+) is an essential molecule in many of these processes and studies have shown that NAD+ deficiency plays a role in disease mechanisms underlying DNA repair disorders such as A-T. NAD+ is available in food, but can also be synthesized in the body from its precursors nicotinamide, nicotinic acid, and nicotinamide riboside (NR), as a group called "vitamin B3". Treatment of experimental A-T animal models with NR showed beneficial effects. The aim of this study is to investigate whether treatment with NR during a period of six months may have positive effects on the disease course of patients with A-T.

Objective: To investigate the effects of NR on the disease course of patients with ataxia telangiectasia.

Study design: Single center, interventional, explorative, open-label proof of concept study.

Study population: Patients with A-T (age >2 years).

Intervention (if applicable): Patients will be treated with nicotinamide riboside (25mg/kg/day), during four consecutive months, followed by a washout period of two months.

Main study parameters/endpoints: Ataxia, dysarthria, quality of life, laboratory parameters.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2

Contacts and Locations

Study Locations

• Netherlands
  • Nijmegen, Netherlands, 6525 GA
    • Radboudumc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 months and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• A-T patients who visit our outpatient clinic.
• Genetically confirmed diagnosis of A-T by the identification of pathogenic mutations of the ATM gene.
• Age ≥ 2 years or older and bodyweight ≥ 12 Kg.
• Informed consent.

Exclusion Criteria:

• Additional medical condition or illness that impair the patient's ability to participate in the study (e.g. actual treatment of a malignancy, active infection, poorly controlled diabetes mellitus, hypertension, organ failure, clinically significant hematological or biochemical abnormalities different from the usual abnormalities in A-T)
• Elevated serum transaminases (> 2 times upper limit of normal)
• Participation in another interventional study at start of the study or during the study
• Pregnancy.
• Breast feeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention group; treatment with vitamin B3	Dietary supplement: Vitamin B3; capsules with niagen; Other Names: Nicotinamide riboside

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ataxia, SARA (Scale of the assesment and rating of ataxia)	Changes in the total score will be measured.	change from baseline -1 month - 4 months - 6 months
Ataxia, ICARS (International Cooperative Ataxia Rating Scale)	Changes in the total score will be measured.	change from baseline -1 month - 4 months - 6 months
Ataxia, 9-hole pegboard test.	Changes in fastes time of the 9-hole pegboard test will be measured.	change from baseline -1 month - 4 months - 6 months
Dysarthria, Radboud dysarthria assesment (RDA)	Changes in maximum performance tasks and severity of dysarthria will be measured.	change from baseline -1 month - 4 months - 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of life questionnaire EuroQoL 5 Dimensions 5 Levels (EQ-5D-5L)	Changes in the total quality of life score will be measured.	change from baseline -1 month - 4 months - 6 months
Laboratory measurements	Results will be summarized descriptively, with abnormal and clinically notable values/findings being identified	change from baseline -1 month - 4 months - 6 months
Intelligibility, Intelligibility in Context Scale (ICS)	Changes in the total score of the Intelligibility in Context Scale (ICS), will be measured.	change from baseline -1 month - 4 months - 6 months
Fatigue, Visual Analogous Scale (VAS)	Changes in the total VAS score will be measured.	change from baseline -1 month - 4 months - 6 months

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Collaborators: A-T Children's Project; Twan foundation (https://twanfoundation.nl)
• Investigators: Principal Investigator: Michel Willemsen, Prof., michel.willemsen@radboudumc.nl

Study record dates

Study Major Dates

• Study Start (Actual): March 18, 2019
• Primary Completion (Actual): December 1, 2019
• Study Completion (Actual): March 1, 2020

Study Registration Dates

• First Submitted: April 11, 2019
• First Submitted That Met QC Criteria: May 22, 2019
• First Posted (Actual): May 23, 2019

Study Record Updates

• Last Update Posted (Actual): July 25, 2022
• Last Update Submitted That Met QC Criteria: July 21, 2022
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: Nicotinamide riboside; Ataxia Telangiectasia; ATM Gene Mutation; ATM protein
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Neurologic Manifestations; Genetic Diseases, Inborn; Dyskinesias; DNA Repair-Deficiency Disorders; Neurocutaneous Syndromes; Cerebellar Diseases; Primary Immunodeficiency Diseases; Spinocerebellar Ataxias; Ataxia; Telangiectasis; Cerebellar Ataxia; Ataxia Telangiectasia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Antimetabolites; Micronutrients; Hypolipidemic Agents; Lipid Regulating Agents; Vitamins; Vitamin B Complex; Nicotinic Acids; Niacinamide; Niacin
• Other Study ID Numbers: NL68197.091.18

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes