Open-label pilot clinical trial of citicoline for fragile X-associated tremor/ataxia syndrome (FXTAS)

PLoS One. 2020 Feb 13;15(2):e0225191. doi: 10.1371/journal.pone.0225191. eCollection 2020.


Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late onset neurodegenerative disorder that is characterized by tremor, cerebellar ataxia, frequent falls, cognitive decline, and progressive loss of motor function. There are currently no approved treatments for this disorder. The purpose of this study was to determine if citicoline was safe for the treatment of tremor and balance abnormalities and to stabilize cognitive decline in patients with FXTAS. Ten participants with diagnosed FXTAS were administered 1000 mg of citicoline once daily for 12 months. Outcome measures and neurological examination were performed at baseline, 3 months, 6 months, and 12 months. The primary outcome was the FXTAS Rating Scale score. Secondary outcomes included change in a battery of neuropsychological tests, an instrumented Timed up and go test, computerized dynamic posturography, 9-hole pegboard test, and balance confidence and psychiatric symptom questionnaires. Safety was also evaluated. Citicoline treatment resulted in minimal adverse events in all but one subject over the course of the study. There was a significant improvement in the Beck Anxiety Inventory (p = 0.03) and the Stroop Color-Word test (p = 0.03), with all other measures remaining stable over the course of 12 months. This open-label pilot trial of citicoline for individuals with FXTAS showed that it is safe and well tolerated in this population. Registration: This trial was registered at Identifier: NCT0219710.

Trial registration: NCT02197104.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Ataxia / diagnosis
  • Ataxia / drug therapy*
  • Cognition / drug effects
  • Cytidine Diphosphate Choline / administration & dosage*
  • Cytidine Diphosphate Choline / adverse effects
  • Female
  • Fragile X Syndrome / diagnosis
  • Fragile X Syndrome / drug therapy*
  • Humans
  • Male
  • Middle Aged
  • Motor Activity / drug effects
  • Neuropsychological Tests
  • Nootropic Agents / administration & dosage*
  • Nootropic Agents / adverse effects
  • Pilot Projects
  • Postural Balance / drug effects
  • Severity of Illness Index
  • Time Factors
  • Time and Motion Studies
  • Treatment Outcome
  • Tremor / diagnosis
  • Tremor / drug therapy*


  • Nootropic Agents
  • Cytidine Diphosphate Choline

Supplementary concepts

  • Fragile X Tremor Ataxia Syndrome

Associated data