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

Sponsor

Hospital de Clinicas de Porto Alegre (Other)

Overall Status

Withdrawn

CT.gov ID

NCT01096095

Collaborator

Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul, Brazil (Other)

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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.

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.

Condition or Disease	Intervention/Treatment	Phase
Spinocerebellar Ataxia Type 3	Drug: Placebo Drug: Sodium Phenylbutyrate	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jun 1, 2010

Anticipated Primary Completion Date :

Dec 1, 2010

Anticipated Study Completion Date :

Jul 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo 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.

Arm

Intervention/Treatment

Placebo Comparator: Placebo

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.

Outcome Measures

Primary Outcome Measures

Safety and tolerability of phenylbutyrate in patients with SCA3 [6 months - 12 months]
The number of adverse events, interruptions and dose reductions in the two groups (cases and controls).

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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.

Exclusion Criteria:

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.