Friedreich’s ataxia MedDRA version: 14.0 Level: PT Classification code 10017374 Term: Friedreich's ataxia System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Trade Name: Nicobion
Product Name: Nicotinamide (Nicobion)
Pharmaceutical Form: Tablet
INN or Proposed INN: Nicotinamide
Other descriptive name: Vitamin B3
Concentration unit: g gram(s)
Concentration
Sponsors
Imperial College
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients must have a molecular genetic diagnosis of FRDA, consisting of a GAA-repeat expansion on both alleles of the FXN gene. 2. FRDA patients over the age of 18 years. 3. Patients must be well enough and willing to provide written informed consent. 4. A female subject is eligible to participate if she is of: • Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MlU/ml and estradiol =65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: 1. Patients with significant clinical dysphagia, 2. Patients taking Sodium Valproate or any other known histone deacetylase inhibitor. 3. Patient’s participating in another clinical trial or who have done so within 30 days before screening. 4. Patients known to be positive for human immunodeficiency virus (HIV). 5. Patients with any additional medical condition or illness that, in the opinion of the Investigator would interfere with study compliance and/or impair the patient's ability to participate or complete the study. Concurrent diseases or conditions that may interfere with study participation or safety include liver disease, bleeding disorders, arrhythmias, organ transplant, organ failure, current neoplasm, poorly controlled diabetes mellitus, poorly controlled hypertension, clinically significant haematological or biochemical abnormality. 6. Patients with a history of substance abuse (e.g. alcohol or drug abuse) within the previous 6 months before enrolment. 7. Patients with a history of severe allergies. 8. Inability to provide informed consent. 9. Female patients who are lactating or pregnant (positive pre-randomisation serum pregnancy test) or plan to become pregnant during the study. 10. Unable or unwilling to provide written informed consent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary aim 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'.;Secondary Objective: The secondary aims are to determine a well-tolerated dose of nicotinamide required to achieve upregulation of Frataxin in FRDA and to gain insight into the way the gene is abnormally regulated and the mechanism whereby nicotinamide might overcome this.;Primary end point(s): Frataxin levels;Timepoint(s) of evaluation of this end point: This is a proof-of-concept dose escalation study. For the single dose study, Frataxin levels will be measured during each of a maximum of 5 visits; separated by a minimum washout of 1 week. For the multiple dose study, having identified either a maximum tolerated dose or a dose that upregulates Frataxin to normal levels, this dose will be given daily for 5 days and daily Frataxin levels measured. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To measure the effect on histone acetylation and methylation at the aberrantly silenced Frataxin gene, chromatin (extracted from blood) will be assessed by immunoprecipitation with antibodies against acetylated histones following nicotinamide administration. In this way we will gain insight into the molecular mechanism whereby nicotinmaide might upregulate Frataxin.;Timepoint(s) of evaluation of this end point: This evaluation will take place following the single-dose escalation after an effective or MTD dose has been identified (visit 5) and again following the multiple dose study after 5 days of oral dosing with nicotinamide at this dose. | — |
Countries
United Kingdom
Contacts
Public ContactFestenstein
Imperial College London
Outcome results
None listed