Effects of Vitamin B3 in Patients With Ataxia Telangiectasia

Ataxia Telangiectasia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03962114
• Other study ID #: NL68197.091.18
• Status: Completed
• Phase: Phase 2
• Start date: March 18, 2019
• Est. completion date: March 1, 2020

Study information

• Verified date: March 2019
• Source: Radboud University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: March 1, 2020
• Est. primary completion date: December 1, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Ataxia
• Ataxia Telangiectasia
• ATM Gene Mutation
• Cerebellar Ataxia
• Telangiectasis

Intervention

Dietary Supplement:
• Vitamin B3
capsules with niagen

Locations

Country	Name	City	State
Netherlands	Radboudumc	Nijmegen

Sponsors (3)

Lead Sponsor	Collaborator
Radboud University Medical Center	A-T Children's Project, Twan foundation (https://twanfoundation.nl)

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Ataxia, ICARS (International Cooperative Ataxia Rating Scale)	Changes in the total score will be measured.	change from baseline -1 month - 4 months - 6 months
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	Fatigue, Visual Analogous Scale (VAS)	Changes in the total VAS score will be measured.	change from baseline -1 month - 4 months - 6 months