Ataxia TelangiectasiaPhase 2NCT03962114
Effects of Vitamin B3 in Patients With Ataxia Telangiectasia
A Phase 2 study testing Vitamin B3 in people with Ataxia Telangiectasia and ATM Gene Mutation, run by Radboud University Medical Center at 1 site in Netherlands.
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. Read more about this study
- Who is it for?
- Ages 2 years and older
- Conditions the study is for
- Ataxia Telangiectasia, ATM Gene Mutation
- What is being tested?
- Vitamin B3
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteNetherlands
- Study dates
- 18 Mar 2019to 1 Mar 2020
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Conditions
- Ataxia Telangiectasia, ATM Gene Mutation
- Being tested
- Vitamin B3
- Keywords
- Ataxia Telangiectasia, ATM Gene Mutation, ATM protein, Nicotinamide riboside
- Medical subject headings
- Ataxia Telangiectasia, Hereditary Sensory and Autonomic Neuropathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vitamin B3Dietary supplement
Also called Nicotinamide riboside
capsules with niagen
| Study group | Role | What they receive |
|---|---|---|
| Intervention group | Experimental | treatment with vitamin B3 Receives: Dietary Supplement: Vitamin B3 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Ataxia, SARA (Scale of the assesment and rating of ataxia)
Changes in the total score will be measured.
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.
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.
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.
Measured: change from baseline -1 month - 4 months - 6 months
Secondary outcomes (4)
Quality of life questionnaire EuroQoL 5 Dimensions 5 Levels (EQ-5D-5L)
Changes in the total quality of life score will be measured.
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
Measured: 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.
Measured: change from baseline -1 month - 4 months - 6 months
Fatigue, Visual Analogous Scale (VAS)
Changes in the total VAS score will be measured.
Measured: change from baseline -1 month - 4 months - 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 May 2019
- Study start18 Mar 2019
- Primary completion1 Dec 2019
- Study completion1 Mar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ataxia TelangiectasiaStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Open label proof of concept study
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- A-T Children's Project, Twan foundation (https://twanfoundation.nl)
- Responsible party
- Sponsor
- Investigators
- Michel Willemsen, Prof., Principal investigator, michel.willemsen@radboudumc.nl
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03962114
- Sponsor's protocol ID
- NL68197.091.18
- Status last verified
- Mar 2019
- First submitted
- 11 Apr 2019
- Last updated
- 25 Jul 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Nicotinamide Riboside (Vitamin B3) in Patients With Ataxia Telangiectasia.
- ClinicalTrials.gov ID
- NCT03962114
- Acronym / sponsor ID
- NL68197.091.18
- Conditions
- Ataxia Telangiectasia, ATM Gene Mutation
- Keywords
- Ataxia Telangiectasia, ATM Gene Mutation, ATM protein, Nicotinamide riboside
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Collaborators
- A-T Children's Project, Twan foundation (https://twanfoundation.nl)
- Study start
- 18 Mar 2019 (actual)
- Primary completion
- 1 Dec 2019 (actual)
- Study completion
- 1 Mar 2020 (actual)
- First posted
- 23 May 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Open label proof of concept study
| Arm | Type | Receives |
|---|---|---|
| Intervention group | Experimental | Dietary Supplement: Vitamin B3treatment with vitamin B3 |
Who may qualify
- Ages
- 2 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Vitamin B3Also: Nicotinamide ribosidecapsules with niagen | Dietary supplement | Intervention group |
Primary outcome
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.
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.
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.
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.
4 secondary outcomes
Quality of life questionnaire EuroQoL 5 Dimensions 5 Levels (EQ-5D-5L)
Time frame: change from baseline -1 month - 4 months - 6 months
Laboratory measurements
Time frame: change from baseline -1 month - 4 months - 6 months
Intelligibility, Intelligibility in Context Scale (ICS)
Time frame: change from baseline -1 month - 4 months - 6 months
Fatigue, Visual Analogous Scale (VAS)
Time frame: change from baseline -1 month - 4 months - 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jul 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michel Willemsen, Prof. principal investigator
michel.willemsen@radboudumc.nl
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Vitamin B3 in people with Ataxia Telangiectasia and ATM Gene Mutation, run by Radboud University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Ataxia, SARA (Scale of the assesment and rating of ataxia) (time frame: change from baseline -1 month - 4 months - 6 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jul 2022.