NAD Supplementation to Prevent Progressive Neurological Disease in Ataxia Telangiectasia

Ataxia Telangiectasia Clinical Trial

Official title:

NAD Supplementation to Prevent Progressive Neurological Disease in Ataxia Telangiectasia

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04870866
• Other study ID #: 2017/419
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: June 5, 2019
• Est. completion date: June 16, 2027

Study information

• Verified date: August 2022
• Source: University Hospital, Akershus
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study investigates the effect of dietary supplementation of nicotinamide ribonucleoside (NR) in children with ataxia telangiectasia (AT), with main focus on neurological symptoms.

Description:

Ataxia Telangiectasia (AT) is a genetic disease, where patients are born with mutations in the Ataxia- Telangiectasia Mutated (ATM) gene. The gene codes for the ATM kinase, which is required for repair of DNA double-stranded breaks and DNA damage response signalling.

There is no treatment available for the neurological manifestations of AT.

The study investigates the effects of NR (300 mg/day) during 2 years.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 13
• Est. completion date: June 16, 2027
• Est. primary completion date: September 3, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years and older

Eligibility

Inclusion Criteria:

• clinically and molecular verified classical A-T disease

Exclusion Criteria:

• less than 2 years of age

• participation in other on-going study

• pregnancy

• liver failure

• other severe medical conditions considered to set patient at risk

Related Conditions & MeSH terms

• Ataxia
• Ataxia Telangiectasia
• Cerebellar Ataxia
• Nervous System Diseases
• Telangiectasis

Intervention

Drug:
• Nicotinamide ribonucleoside
Two year intervention

Locations

Country	Name	City	State
Norway	Hilde Loge Nilsen	Lørenskog
Norway	Oslo University Hospital	Oslo

Sponsors (9)

Lead Sponsor	Collaborator
University Hospital, Akershus	Haukeland University Hospital, Oslo University Hospital, South-Eastern Norway Regional Health Authority, St. Olavs Hospital, Sykehuset Innlandet HF, The Bergesen Foundation, University Hospital of North Norway, University of Bergen

Country where clinical trial is conducted

Norway, 

References & Publications (1)

Fang EF, Kassahun H, Croteau DL, Scheibye-Knudsen M, Marosi K, Lu H, Shamanna RA, Kalyanasundaram S, Bollineni RC, Wilson MA, Iser WB, Wollman BN, Morevati M, Li J, Kerr JS, Lu Q, Waltz TB, Tian J, Sinclair DA, Mattson MP, Nilsen H, Bohr VA. NAD(+) Replenishment Improves Lifespan and Healthspan in Ataxia Telangiectasia Models via Mitophagy and DNA Repair. Cell Metab. 2016 Oct 11;24(4):566-581. doi: 10.1016/j.cmet.2016.09.004. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	NAD metabolome	Increase of NAD+ and other stable NAD+ metabolites (referred to as the NAD metabolome) in blood	2 years
Secondary	Patient well being	Improved or stabilized health-related quality of life (HRQOL) measured with the Pediatric Quality of Life Inventory (PedSQL)	2 years
Secondary	Motoric function - The Scale for the Assessment and Rating of Ataxia (SARA)	Stabilized motoric function measured with SARA.; The SARA scale is made up of measurements related to gait, stance, sitting, speech, finger-chase test, nose-finger test, fast alternating movements and heel-shin test.; The range is from no ataxia (value 0) to severe ataxia (value 40).	2 years
Secondary	Motoric function - The International Cooperative Ataxia Rating Scale (ICARS)	Stabilized motoric function measured with ICARS.; The ICARS scale is made from measurements of postural and gait disturbances, limb ataxia, dysarthria, and oculomotor disorders.; The range is from no ataxia (value 0) to severe ataxia (value 100).	2 years
Secondary	Motoric function - Customized gait scale (GS)	Stabilized motoric function measured with GS.; The gait scale assess gait functionality in patients with Ataxia-telangiectasia.; The range is from no walking ability (value 0) to normal walking ability according to age and maturity (value 10).	2 years
Secondary	Motoric function - AT Neuro Examination Scale Toolkit, updated version (AT-NEST)	Stabilized motoric function measured with AT-NEST.; The AT-NEST scale is made from scoring of speech, handwriting/drawing, oculomotor, ataxia, muscle strength, neuropathy, growth, nutrition, learning ability/cognition, MS mental state.; The range is from normal (value 144) to severe ataxia (value 0).	2 years
Secondary	Motoric function - Clinical Global Scale rating instrument for A-T	Stabilized motoric function measured with Clinical Global Scale rating instrument for A-T.; The Clinical Global Scale rating instrument for A-T scale is made from scoring of gait ataxia, dysmetria, dysarthria, extrapyramidal movements and eye movements.; The range is from normal (value 0) to severe (value 4).	2 years
Secondary	Liver function	Normalized or stabilized liver function as assessed by blood levels of; -alfa fetoprotein (AFP)	2 years
Secondary	Blood sugar control	Normalized or stabilized blood sugar levels as measured in blood: -HbA1c	2 years
Secondary	Mitochondrial function	Normalized or stabilized mitochondrial markers in blood: lactate; lactate dehydrogenase; FGF21	2 years