Pilot Study of Safety and Efficacy of Sodium Phenylbutyrate in Spinocerebellar Ataxia Type 3

NCT01096095 | Withdrawn Phase 2

• 1 other identifier: CONEP CAAE 0527.0.001.000-07
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

DESIGN: Pilot, Phase II, double-blind, placebo-controlled study JUSTIFICATION: In the literature one does not find a pharmacological treatment that changes the natural history of Spinocerebellar ataxtia type 3 (SCA3). Patients with this disease invariably become dependent. OBJECTIVES I. To determine safety and tolerability of phenylbutyrate in patients with SCA3. II. To provide early subsidies on the efficacy of phenylbutyrate in SCA3. DURATION: 12 months of a double-blind study. PLACE OF REALIZATION: Hospital de Clínicas de Porto Alegre, Brazil. NUMBER OF PATIENTS: 20 patients. CONCOMITANT MEDICATIONS: There are no concomitant medications that are prohibited unless they affect safety parameters of this study (hemogram and platelets; fasting serum glucose, AST, ALT, Gamma-GT, Bilirubins, Prothrombin time, Creatinine, Urea, Na, K, chlorides and arterial gasometry; electrocardiogram and echocardiogram). MEDICATIONS UNDER INVESTIGATION: Powdered sodium phenylbutyrate in sachets containing each 3g. At the start of the study, the dose will be 15g/day (five sachets) and may be reduced in case of mild adverse events. OUTCOMES Primary safety outcome: The number of adverse events, interruptions and dose reductions in the two groups (cases and controls). Efficacy outcomes: Efficacy outcomes are the following scores in both groups: NESSCA, SARA, Barthel, BDI, and WHOQol.

Conditions

Spinocerebellar Ataxia Type 3

Keywords

SCA; Spinocerebellar Ataxia; Sodium Phenylbutyrate; Machado-Joseph Disease; Treatment

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability of phenylbutyrate in patients with SCA3

  The number of adverse events, interruptions and dose reductions in the two groups (cases and controls).

  6 months - 12 months

Secondary Outcomes (1)

• Efficacy of phenylbutyrate in SCA3 on neurological dysfunction and quality of life

  6 months - 12 months

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Sodium phenylbutyrate

EXPERIMENTAL

Active drug

Drug: Sodium Phenylbutyrate

Interventions

Placebo DRUG

Powdered placebo in sachets containing each 3g. At the start of the study, the dose will be 15g/day (five sachets).

Placebo

Sodium Phenylbutyrate DRUG

Powdered sodium phenylbutyrate in sachets containing each 3g. At the start of the study, the dose will be 15g/day (five sachets) and may be reduced in case of mild adverse events.

Sodium phenylbutyrate

Eligibility Criteria

• Age: 16 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• All patients shall have their molecular diagnosis confirmed and expanded polyglutamine tract (CAG) measures already determined.
• Patients still able to walk with until 8 years of disease duration, and
• Patients aged 16 years or over will be invited to participate in the study.

You may not qualify if:

• they show electrocardiogram ou echocardiographic alterations suggestive of heart insufficiency at baseline;
• their serum creatinine levels are higher than 1.2 mg/dL, with the confirmation of renal insufficiency due to the rate of glomerular filtration;
• they show a history of hypersensibility to sodium phenylbutyrate, and if
• they (men and women) do not agree to use a reliable contraceptive method during the entire study period and for three months after its end.

Sponsors & Collaborators

• Hospital de Clinicas de Porto Alegre: lead
• Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul, Brazil: collaborator

Study Sites (1)

Hospital de Clínicas de Porto Alegre

Porto Alegre, Rio Grande do Sul, 90.035-903, Brazil

Location

MeSH Terms

Conditions

Machado-Joseph Disease; Spinocerebellar Ataxias

Interventions

4-phenylbutyric acid

Condition Hierarchy (Ancestors)

Cerebellar Ataxia; Cerebellar Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Spinocerebellar Degenerations; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Ataxia; Dyskinesias; Neurologic Manifestations; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Laura B Jardim, PhD

  Medical Genetics Service of Hospital de Clínicas de Porto Alegre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 29, 2010
• First Posted: March 30, 2010
• Study Start: June 1, 2010
• Primary Completion: December 1, 2010
• Study Completion: July 1, 2011
• Last Updated: August 17, 2012

Record last verified: 2010-05

Locations

BR (1)