A Double-Blind Cross-over Trial of Amantadine Hydrochloride in Friedreich's Ataxia

ABSTRACT:We performed a double-blind cross-over study with amantadine hydrochloride in 12 patients with Friedreich's disease and 2 with autosomal dominant cerebellar ataxia. Patients were randomly assigned to a placebo-amantadine or amantadine-placebo sequence. The interval between the treatments was two weeks. Patients were graded according to a functional ataxia scoring scale and videotaped in basal conditions and 90 min after a single oral dose of 100 mg amantadine or placebo. Three evaluators independently scored the videotapes. Statistical analysis showed no significant effect of amantadine in Friedreich's disease.

Download Full-text

A Controlled Study of Oral Vigabatrin (ɣ-Vinyl GABA) in Patients with Cerebellar Ataxia

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100036672 ◽

1986 ◽

Vol 13 (4) ◽

pp. 331-333 ◽

Cited By ~ 7

Author(s):

A.M. Bonnet ◽

M. Esteguy ◽

G. Tell ◽

P.J. Schechter ◽

J. Hardenberg ◽

...

Keyword(s):

Cerebellar Ataxia ◽

Friedreich’S Ataxia ◽

Friedreich's Ataxia ◽

Controlled Study ◽

Olivopontocerebellar Atrophy ◽

Irreversible Inhibitor ◽

Double Blind ◽

Double Blind Placebo ◽

Significant Difference ◽

Daily Dose

ABSTRACT:Vigabatrin (ɣ-vinyl GABA; GVG), an irreversible inhibitor of GABA-transaminase, at a daily dose of 2-4 g, and a placebo were each administered orally for 4 months to 14 patients with cerebellar ataxia (9 with Friedreich's ataxia, 5 with olivopontocerebellar atrophy), in a double-blind, placebo-controlled crossover study. For the group as a whole, there was no significant difference between the GVG and placebo periods in any of the parameters of cerebellar symptomatology measured. Individually, one patient showed some improvement after 3 months of treatment with 2 g/day GVG. Tolerance to 4 g/day GVG was poor, whereas 2 g/day was well tolerated. The results suggest that agents which increase central GABA concentrations are not likely to be of benefit to patients with Friedreich's ataxia or olivopontocerebellar atrophy.

Download Full-text

Spinocerebellar ataxia type 28: A novel autosomal dominant cerebellar ataxia characterized by slow progression and ophthalmoparesis

The Cerebellum ◽

10.1007/s12311-008-0053-9 ◽

2008 ◽

Vol 7 (2) ◽

pp. 184-188 ◽

Cited By ~ 42

Author(s):

Caterina Mariotti ◽

Alfredo Brusco ◽

Daniela Di Bella ◽

Claudia Cagnoli ◽

Marco Seri ◽

...

Keyword(s):

Cerebellar Ataxia ◽

Spinocerebellar Ataxia ◽

Autosomal Dominant ◽

Autosomal Dominant Cerebellar Ataxia ◽

Spinocerebellar Ataxia Type ◽

Slow Progression

Download Full-text

Effect of a Single Oral Dose of Glutamine on Cardiac Performance during Exercise in Patients with Stable Angina Pectoris: A Double Blind Study

Clinical Science ◽

10.1042/cs099015pa ◽

2000 ◽

Vol 99 (s43) ◽

pp. 15P-15P

Author(s):

Seo Khogali ◽

SD Pringle ◽

B Weryk ◽

EM Connolly ◽

JA Lyall ◽

...

Keyword(s):

Angina Pectoris ◽

Oral Dose ◽

Single Oral Dose ◽

Stable Angina ◽

Cardiac Performance ◽

Blind Study ◽

Double Blind Study ◽

Stable Angina Pectoris ◽

Double Blind

Download Full-text

Thorough QT Study to Evaluate the Effect of Zoliflodacin, a Novel Therapeutic for Gonorrhea, on Cardiac Repolarization in Healthy Adults

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01292-21 ◽

2021 ◽

Author(s):

Lori M. Newman ◽

Martin Kankam ◽

Aya Nakamura ◽

Tom Conrad ◽

John Mueller ◽

...

Keyword(s):

Oral Dose ◽

Single Oral Dose ◽

Cardiac Repolarization ◽

Cardiac Safety ◽

Double Blind ◽

Thorough Qt Study ◽

Regulatory Guidelines ◽

Clinically Significant ◽

The One ◽

Global Threat

Zoliflodacin is a novel spiropyrimidinetrione antibiotic being developed as single oral dose treatment to address the growing global threat of Neisseria gonorrhoeae . To evaluate the cardiac safety of zoliflodacin, a thorough QT/QTc (TQT) study was performed in healthy subjects. In this randomized, double-blind, placebo-controlled, 4-period crossover study, 72 subjects in a fasted state received a single dose of zoliflodacin 2 g (therapeutic), zoliflodacin 4 g (supratherapeutic), placebo, and moxifloxacin 400 mg as a positive comparator. Cardiac repolarization was measured by duration of the corrected QT interval by Fridericia’s formula (QTcF). At each time point up to 24 hours after zoliflodacin administration, the upper limit of the one-sided 95% confidence interval (CI) for the placebo-corrected change from the pre-dose baseline in QTcF (ΔΔQTcF) was less than 10 ms, indicating an absence of a clinically meaningful increase in QT prolongation. The lower limit of the one-sided multiplicity-adjusted 95% CI of ΔΔQTcF for moxifloxacin was longer than 5 ms at four time points from 1-4 hours after dosing, demonstrating adequate sensitivity of the QTc measurement. There were no clinically significant effects on heart rate, PR and QRS intervals, ECG morphology, or laboratory values. Treatment-emergent adverse events (AEs) were mild or moderate in severity and transient. This was a negative TQT study according to regulatory guidelines (E14) and confirms that a single oral dose of zoliflodacin is safe and well-tolerated. These findings suggest zoliflodacin is not proarrhythmic and contribute to the favorable assessment of cardiac safety for a single oral dose of zoliflodacin.

Download Full-text