NCT01589809

Effect of Nicotinamide in Friedreich's Ataxia

Pharmacodynamic Studies of a Histone Deacetylase Inhibitor in Friedreich's Ataxia

• Status: Unknown
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Sponsor: Imperial College London · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Accepted

Summary

The purpose of the interventional study is to determine whether Nicotinamide is effective at upregulating the Frataxin (FXN) gene in patients with Friedreich's ataxia (FRDA) where this gene is abnormally 'switched off'. The purpose of the non-interventional study is to investigate the use of novel, highly-sensitive technology to capture clinical deficit and measure subtle changes in the activities of daily living and to correlate functional changes to levels of expression of Frataxin protein and the epigenetic structure of the Frataxin gene over a 9-12 month period without nicotinamide. Healthy volunteers will be included as comparators in this part of the study.

Detailed description

Friedreich's ataxia (FRDA) is caused by a GAA repeat expansion in the Frataxin gene causing its repression which resembles the archetypal epigenetic phenomenon of Position Effect Variegation and hence can be modulated by chromatin modifiers The investigators have now confirmed that a similar form of silencing occurs in cells from FRDA patients. Based on these findings histone deacetylase (HDAC) inhibitors which can overcome such silencing have been identified. The investigators have extended this result by showing that the classical Class III HDAC inhibitor, nicotinamide, can relieve silencing in cells from patients. Nicotinamide is a vitamin and a registered drug and has been previously administered to humans with no significant ill effects. In the interventional study, the investigators will perform pharmacodynamic studies on nicotinamide in humans with FRDA to investigate whether the investigators can upregulate Frataxin and if so, to determine an optimum dosing regimen. Nicotinamide will be administered orally following a standard drug escalation regimen and blood samples taken to measure Frataxin level and chromatin structure of the Frataxin gene. The end-point of the study is to achieve significant upregulation of Frataxin in patients providing a potential therapy for this currently untreatable condition. In the non-interventional study, we will investigate the use of novel, highly-sensitive technology to capture clinical deficit and measure subtle changes in the activities of daily living and correlate functional changes to levels of expression of Frataxin protein and the epigenetic structure of the Frataxin gene over a 9-12 month period without nicotinamide. Healthy volunteers as comparators will be included in this part of the study. HVs will undergo the same assessments as participants with Friedreich ataxia once.

Conditions

• Neurodegenerative Disorders

Interventions

Type	Name	Description
DRUG	nicotinamide	dose-escalation, 2-8 grams, oral

Timeline

• Start date: 2012-06-01
• Primary completion: 2015-06-01
• Completion: 2017-12-01
• First posted: 2012-05-02
• Last updated: 2017-07-02

Locations

2 sites across 1 country: United Kingdom