The effects of etidronate on brain calcifications in Fahr's disease or syndrome: rationale and design of the randomised, placebo-controlled, double-blind CALCIFADE trial

Birgitta Mg Snijders*, Gini Mathijssen, Mike Jl Peters, Marielle H Emmelot-Vonk, Pim A de Jong, Susan Bakker, Heleen A Crommelin, Ynte M Ruigrok, Eva H Brilstra, Vera Pm Schepers, Wilko Spiering, Evelien van Valen, Huiberdina L Koek

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

BACKGROUND: Fahr's disease and syndrome are rare disorders leading to calcification of the small arteries in the basal ganglia of the brain, resulting in a wide range of symptoms comprising cognitive decline, movement disorders and neuropsychiatric symptoms. No disease-modifying therapies are available. Studies have shown the potential of treatment of ectopic vascular calcifications with bisphosphonates. This paper describes the rationale and design of the CALCIFADE trial which evaluates the effects of etidronate in patients with Fahr's disease or syndrome.

METHODS: The CALCIFADE trial is a randomised, placebo-controlled, double-blind trial which evaluates the effects of etidronate 20 mg/kg during 12 months follow-up in patients aged ≥ 18 years with Fahr's disease or syndrome. Etidronate and placebo will be administered in capsules daily for two weeks on followed by ten weeks off. The study will be conducted at the outpatient clinic of the University Medical Center Utrecht, the Netherlands. The primary endpoint is the change in cognitive functioning after 12 months of treatment. Secondary endpoints are the change in mobility, neuropsychiatric symptoms, volume of brain calcifications, dependence in activities of daily living, and quality of life.

RESULTS: Patient recruitment started in April 2023. Results are expected in 2026 and will be disseminated through peer-reviewed journals as well as presentations at national and international conferences.

CONCLUSIONS: Fahr's disease and syndrome are slowly progressive disorders with a negative impact on a variety of health outcomes. Etidronate might be a new promising treatment for patients with Fahr's disease or syndrome.

TRIAL REGISTRATION: ClinicalTrials.gov, NCT05662111. Registered 22 December 2022, https://clinicaltrials.gov/ct2/show/NCT01585402 .

Original languageEnglish
Article number49
Number of pages8
JournalOrphanet Journal of Rare Diseases
Volume19
Issue number1
DOIs
Publication statusPublished - 7 Feb 2024

Keywords

  • Activities of Daily Living
  • Basal Ganglia Diseases/complications
  • Brain
  • Calcinosis
  • Etidronic Acid/therapeutic use
  • Humans
  • Neurodegenerative Diseases
  • Quality of Life
  • Brain calcifications
  • Randomised-controlled trial
  • Fahr’s syndrome
  • Cognitive functioning
  • Etidronate
  • Fahr’s disease
  • Primary Familial Brain Calcification

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