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

Phenylbutyrate in SCA3: a Double-blind, Placebo-controlled Study to Determine Safety and Efficacy of Sodium Phenylbutyrate in Patients With SCA3

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.

Study Overview

• Status: Withdrawn
• Conditions: Spinocerebellar Ataxia Type 3
• Intervention / Treatment: Drug: Placebo; Drug: Sodium Phenylbutyrate

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90.035-903
      • Hospital de Clinicas de Porto Alegre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 76 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

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

Exclusion Criteria:

1. they show electrocardiogram ou echocardiographic alterations suggestive of heart insufficiency at baseline;
2. their serum creatinine levels are higher than 1.2 mg/dL, with the confirmation of renal insufficiency due to the rate of glomerular filtration;
3. they show a history of hypersensibility to sodium phenylbutyrate, and if
4. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Powdered placebo in sachets containing each 3g. At the start of the study, the dose will be 15g/day (five sachets).
Experimental: Sodium phenylbutyrate; Active drug	Drug: Sodium Phenylbutyrate; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of phenylbutyrate in SCA3 on neurological dysfunction and quality of life	Efficacy outcomes are the following scores in both groups: NESSCA, SARA, 9-hole peg board test, BDI, and WHOQol.	6 months - 12 months

Collaborators and Investigators

• Sponsor: Hospital de Clinicas de Porto Alegre
• Collaborators: Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul, Brazil
• Investigators: Principal Investigator: Laura B Jardim, PhD, Medical Genetics Service of Hospital de Clínicas de Porto Alegre

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (Anticipated): December 1, 2010
• Study Completion (Anticipated): July 1, 2011

Study Registration Dates

• First Submitted: March 29, 2010
• First Submitted That Met QC Criteria: March 29, 2010
• First Posted (Estimate): March 30, 2010

Study Record Updates

• Last Update Posted (Estimate): August 17, 2012
• Last Update Submitted That Met QC Criteria: August 15, 2012
• Last Verified: May 1, 2010

More Information

Terms related to this study

• Keywords: Treatment; Spinocerebellar Ataxia; SCA; Sodium Phenylbutyrate; Machado-Joseph Disease
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Genetic Diseases, Inborn; Neurodegenerative Diseases; Dyskinesias; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Cerebellar Diseases; Ataxia; Cerebellar Ataxia; Spinocerebellar Ataxias; Spinocerebellar Degenerations; Machado-Joseph Disease; Antineoplastic Agents; 4-phenylbutyric acid
• Other Study ID Numbers: CONEP CAAE 0527.0.001.000-07