Treatment for calcification issues in Fahr's disease

A Randomized, Placebo-controlled, Double-blind Trial to Study the Effects of Etidronate on Ectopic CALCIfication in FAhr's Disease or Syndrome

This study is testing if a medication called etidronate can help improve brain symptoms in people with Fahr's disease, which causes calcium buildup in the brain.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 98 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: UMC Utrecht (Academic / other)
• Locations: 2 sites (Utrecht, Utrecht and 1 other locations)
• Trial ID: NCT05662111 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effectiveness of bisphosphonates, specifically etidronate, in treating patients diagnosed with Fahr's disease or syndrome, which is characterized by calcifications in the brain. The study aims to assess the impact of this treatment on the neuropsychiatric and cognitive symptoms associated with the condition. Participants will be randomly assigned to receive either etidronate or a placebo, with their progress monitored over the course of the trial. The goal is to provide a potential disease-modifying therapy for a condition that currently lacks effective treatments.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 and over with a clinical diagnosis of Fahr's disease or syndrome and confirmed bilateral calcifications in the basal ganglia.

Not a fit: Patients with calcifications due to aging or other secondary causes of brain calcifications may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve the quality of life and functional independence of patients suffering from Fahr's disease or syndrome.

How similar studies have performed: Previous small case series have shown that bisphosphonates may be effective in treating Fahr's disease, suggesting potential for success in this larger, controlled trial.

Eligibility criteria

Inclusion criteria are:

1. Age of 18 years or over,
2. Clinical diagnosis of Fahr's disease or syndrome. No international accepted diagnostic criteria for Fahr's disease or syndrome exist yet. It is diagnosed mostly based on the clinical presentation. For the present study the following criteria are used:

   1. Clinical symptoms consistent with a clinical diagnosis of Fahr's disease or syndrome.
   2. Bilateral calcifications of the basal ganglia as seen on the computed tomography (CT) scan of the head. To rule out basal ganglia calcifications due to aging, a CT based calcification score will be used as proposed by Nicolas et al. Calcification is graded from 0 (no calcification) to 5 (serious and confluent) in specific locations of the brain; lenticular, caudate, thalamus nuclei, subcortical white matter, cortex, cerebellar hemispheres, vermis, midbrain, pons, and medulla. The total calcification score (ranging from 0 to 80) is obtained by adding all location-specific points, where a score higher than the age-specific threshold points at Fahr's disease or syndrome.

      Furthermore, the next criteria are supportive for the clinical diagnosis of PFBC:
   3. Frequently, the family history is consistent with autosomal dominant inheritance. A positive family history with at least one relative in the first or second degree with symptoms of PFBC is supportive for the clinical diagnosis of PFBC.
   4. The presence of a (likely) pathogenic mutation in one of the PFBC-related genes is supportive for the clinical diagnosis of PFBC. Mutations in up to now 4 known genes are associated with an autosomal dominant pattern of inheritance: solute carrier family 20 member 2 (SLC20A2) (OMIM#213600), xenotropic and polytropic retrovirus receptor 1 (XPR1) (OMIM#616413), platelet-derived growth factor b (PDGFB) (OMIM#615483), and platelet-derived growth factor receptor b (PDGFRB) (OMIM#615007). Autosomal recessively inherited PFBC is associated with mutations in two genes: myogenesis-regulating glycosidase (MYORG) (OMIM#618317) and junctional adhesion molecule 2 (JAM2) (OMIM#618824).

Exclusion criteria are:

1. unable or unwilling to sign an informed consent,
2. severe renal impairment (estimated glomerular filtration rate (eGFR) of \<30 ml/min/1.73m2 calculated using CKD-EPI equation),
3. contraindication to receiving oral medication (for example severe dysphagia),
4. known abnormality of the oesophagus that would interfere with the passage of the drug (for example oesophageal strictures or achalasia),
5. known sensitivity to etidronate,
6. pregnancy, women with an active pregnancy wish \<1 year, or women who are breastfeeding at the time of inclusion,
7. inability to undergo a Dutch neuropsychological assessment (for example, non-fluent Dutch speakers or severe visual, hearing or motor impairment),
8. any other medical or social condition that puts the subject at risk of harm during the study or might adversely affect the interpretation of the study data,
9. use of bisphosphonates during the last 5 years,
10. hypocalcaemia (calcium \<2.20 mmol/L),
11. 25-OH vitamin D deficiency \<35 nmol/L. After correction of hypocalcaemia or vitamin D deficiency, a participant is again suitable for participation.

Where this trial is running

Utrecht, Utrecht and 1 other locations

• University Medical Center Utrecht — Utrecht, Utrecht, Netherlands (Recruiting)
• University College London Hospital — London, United Kingdom (Not_yet_recruiting)

Study contacts

• Principal investigator: Huiberdina L Koek, MD, PhD — UMC Utrecht
• Study coordinator: Huiberdina L Koek, MD PhD

Conditions Fahr Disease; Fahr Syndrome; Primary Familial Brain Calcification