Filla 1988.

Methods	Double‐blind, placebo‐controlled, cross‐over study using an ABCB design
Participants	17 participants with Friedreich ataxia (not genetically confirmed) (8 female, 9 male, mean age 23.4 years (± 8.1 years)) and 14 participants with other SCAs (6 female, 8 male, mean age 47.1 years (± 13.4 years)) including: 10 with autosomal dominant cerebellar ataxia, 2 with idiopathic late onset cerebellar ataxia (not genetically confirmed), 1 with autosomal recessive late onset cerebellar ataxia (no formal diagnosis) and 1 with early onset cerebellar ataxia with retained tendon reflexes (not genetically confirmed)
Interventions	Thyrotropin‐releasing hormone tartrate (TRH‐T) or placebo were administered intramuscularly. There were 2 sequences (groups of participants) within the study: sequence I began the study in the placebo arm, sequence II in the active treatment arm (TRH‐T). 9 participants with Friedreich ataxia and 6 participants with SCA underwent sequence I (1st month with placebo). 7 participants with Friedreich ataxia and 9 participants with SCA underwent sequence II (1st month with TRH 2 mg). Each treatment was administered for 1 month in a double cross‐over design. Participants were allocated randomly to either sequence. The daily dose of TRH‐T was 2 mg for the 1st month and 4 mg for the 2nd active treatment phase
Outcomes	Neurological and clinical function were evaluated using the Inherited Ataxias Clinical Rating Scale (IACRS) which contains a speech component. The study neurologist, blinded to the treatment condition, evaluated speech subjectively using a categorical scale where 0 reflected 'normal' function and 4 was considered 'not understandable'
Notes	6 participants remained on their pre‐existing pharmaceutical treatment regime throughout the experiment. Diagnosis was not genetically confirmed for the cohort as the genes for the respective disorders had not yet been identified (Campuzano 1996; Orr 1993) Cyanamid Italia, Italy provided TRH‐T and matching placebo
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Participants were randomly allocated to TRH‐T or placebo. Given the relatively even distribution of participants with Friedreich ataxia and SCA in the 2 groups, the random nature of the selection is unclear
Allocation concealment (selection bias)	Unclear risk	Not stated
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Participants blinded to treatment condition
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Assessor blinded to treatment condition. The same experimenter conducted the assessments over the course of the trial
Selective reporting (reporting bias)	Low risk	All planned outcomes reported
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	1 participant in the Friedreich ataxia group dropped out
Other bias	Unclear risk	Dose strength was not randomised (2 mg in the 1st treatment phase and 4 mg in the 2nd)