免费获得国外相关药品，最快 1 个工作日回馈药物信息
Effects of 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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Ataxia Telangiectasia ATM Gene Mutation | Dietary Supplement: Vitamin B3 | Phase 2 |
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 (Clinical Trial) |
| Actual Enrollment : | 24 participants |
| Allocation: | N/A |
| 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
|
- 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.
- 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.
- 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
- 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.
- 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.
| Ages Eligible for Study: | 2 Years and older (Child, Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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.
| Netherlands | |
| Radboudumc | |
| Nijmegen, Netherlands, 6525 GA | |
| Principal Investigator: | Michel Willemsen, Prof. | michel.willemsen@radboudumc.nl |
| Tracking Information | |||||||
|---|---|---|---|---|---|---|---|
| First Submitted Date ICMJE | April 11, 2019 | ||||||
| First Posted Date ICMJE | May 23, 2019 | ||||||
| Last Update Posted Date | May 23, 2019 | ||||||
| Actual Study Start Date ICMJE | March 18, 2019 | ||||||
| Estimated Primary Completion Date | December 1, 2019 (Final data collection date for primary outcome measure) | ||||||
| Current Primary Outcome Measures ICMJE |
|
||||||
| Original Primary Outcome Measures ICMJE | Same as current | ||||||
| Change History | No Changes Posted | ||||||
| Current Secondary Outcome Measures ICMJE |
|
||||||
| Original Secondary Outcome Measures ICMJE | Same as current | ||||||
| Current Other Pre-specified Outcome Measures | Not Provided | ||||||
| Original Other Pre-specified Outcome Measures | Not Provided | ||||||
| Descriptive Information | |||||||
| Brief Title ICMJE | Effects of Vitamin B3 in Patients With Ataxia Telangiectasia | ||||||
| Official Title ICMJE | Effects of Nicotinamide Riboside (Vitamin B3) in Patients With Ataxia Telangiectasia. | ||||||
| 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. |
||||||
| 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 ICMJE | Interventional | ||||||
| Study Phase ICMJE | Phase 2 | ||||||
| Study Design ICMJE | Allocation: N/A Intervention Model: Single Group Assignment Intervention Model Description: Open label proof of concept study Masking: None (Open Label)Primary Purpose: Treatment |
||||||
| Condition ICMJE |
|
||||||
| Intervention ICMJE | Dietary Supplement: Vitamin B3
capsules with niagen
Other Name: Nicotinamide riboside
|
||||||
| Study Arms ICMJE | Experimental: Intervention group
treatment with vitamin B3
Intervention: Dietary Supplement: Vitamin B3
|
||||||
| Publications * | Not Provided | ||||||
|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
|||||||
| Recruitment Information | |||||||
| Recruitment Status ICMJE | Unknown status | ||||||
| Actual Enrollment ICMJE |
24 | ||||||
| Original Actual Enrollment ICMJE | Same as current | ||||||
| Estimated Study Completion Date ICMJE | March 1, 2020 | ||||||
| Estimated Primary Completion Date | December 1, 2019 (Final data collection date for primary outcome measure) | ||||||
| Eligibility Criteria ICMJE |
Inclusion Criteria:
Exclusion Criteria:
|
||||||
| Sex/Gender ICMJE |
|
||||||
| Ages ICMJE | 2 Years and older (Child, Adult, Older Adult) | ||||||
| Accepts Healthy Volunteers ICMJE | No | ||||||
| Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | ||||||
| Listed Location Countries ICMJE | Netherlands | ||||||
| Removed Location Countries | |||||||
| Administrative Information | |||||||
| NCT Number ICMJE | NCT03962114 | ||||||
| Other Study ID Numbers ICMJE | NL68197.091.18 | ||||||
| Has Data Monitoring Committee | No | ||||||
| U.S. FDA-regulated Product |
|
||||||
| IPD Sharing Statement ICMJE |
|
||||||
| Responsible Party | Radboud University | ||||||
| Study Sponsor ICMJE | Radboud University | ||||||
| Collaborators ICMJE |
|
||||||
| Investigators ICMJE |
|
||||||
| PRS Account | Radboud University | ||||||
| Verification Date | March 2019 | ||||||
|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |
|||||||
