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Effects of Vitamin B3 in Patients With Ataxia Telangiectasia

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ClinicalTrials.gov Identifier: NCT03962114
Recruitment Status : Enrolling by invitation
First Posted : May 23, 2019
Last Update Posted : May 23, 2019
Sponsor:
Collaborators:
A-T childrens project
Twan foundation
Information provided by (Responsible Party):
Radboud University

Brief 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.


Condition or disease Intervention/treatment Phase
Ataxia Telangiectasia ATM Gene Mutation Dietary Supplement: Vitamin B3 Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Intervention Model: Single Group Assignment
Intervention Model Description: Open label proof of concept study
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Effects of Nicotinamide Riboside (Vitamin B3) in Patients With Ataxia Telangiectasia.
Actual Study Start Date : March 18, 2019
Estimated Primary Completion Date : December 1, 2019
Estimated Study Completion Date : March 1, 2020


Arm Intervention/treatment
Experimental: Intervention group
treatment with vitamin B3
Dietary Supplement: Vitamin B3
capsules with niagen
Other Name: Nicotinamide riboside




Primary Outcome Measures :
  1. Ataxia, SARA (Scale of the assesment and rating of ataxia) [ Time Frame: change from baseline -1 month - 4 months - 6 months ]
    Changes in the total score will be measured.

  2. Ataxia, ICARS (International Cooperative Ataxia Rating Scale) [ Time Frame: change from baseline -1 month - 4 months - 6 months ]
    Changes in the total score will be measured.

  3. Ataxia, 9-hole pegboard test. [ Time Frame: change from baseline -1 month - 4 months - 6 months ]
    Changes in fastes time of the 9-hole pegboard test will be measured.

  4. Dysarthria, Radboud dysarthria assesment (RDA) [ Time Frame: change from baseline -1 month - 4 months - 6 months ]
    Changes in maximum performance tasks and severity of dysarthria will be measured.


Secondary Outcome Measures :
  1. Quality of life questionnaire EuroQoL 5 Dimensions 5 Levels (EQ-5D-5L) [ Time Frame: change from baseline -1 month - 4 months - 6 months ]
    Changes in the total quality of life score will be measured.

  2. Laboratory measurements [ Time Frame: change from baseline -1 month - 4 months - 6 months ]
    Results will be summarized descriptively, with abnormal and clinically notable values/findings being identified

  3. Intelligibility, Intelligibility in Context Scale (ICS) [ Time Frame: change from baseline -1 month - 4 months - 6 months ]
    Changes in the total score of the Intelligibility in Context Scale (ICS), will be measured.

  4. Fatigue, Visual Analogous Scale (VAS) [ Time Frame: change from baseline -1 month - 4 months - 6 months ]
    Changes in the total VAS score will be measured.



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Ages Eligible for Study:   2 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03962114


Locations
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Netherlands
Radboudumc
Nijmegen, Netherlands, 6525 GA
Sponsors and Collaborators
Radboud University
A-T childrens project
Twan foundation
Investigators
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Principal Investigator: Michel Willemsen, Prof. michel.willemsen@radboudumc.nl

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Responsible Party: Radboud University
ClinicalTrials.gov Identifier: NCT03962114     History of Changes
Other Study ID Numbers: NL68197.091.18
First Posted: May 23, 2019    Key Record Dates
Last Update Posted: May 23, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Radboud University:
Ataxia Telangiectasia
ATM Gene Mutation
ATM protein
Nicotinamide riboside
Additional relevant MeSH terms:
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Ataxia
Cerebellar Ataxia
Ataxia Telangiectasia
Spinocerebellar Ataxias
Telangiectasis
Dyskinesias
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Cerebellar Diseases
Brain Diseases
Central Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Neurocutaneous Syndromes
Genetic Diseases, Inborn
DNA Repair-Deficiency Disorders
Metabolic Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Vitamins
Niacinamide
Niacin
Nicotinic Acids
Vitamin B Complex
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs
Hypolipidemic Agents