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

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.

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

• Placebo Comparator: Placebo
  Placebo
  Intervention: Drug: Placebo
• Experimental: Sodium phenylbutyrate
  Active drug
  Intervention: Drug: Sodium Phenylbutyrate

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.