A randomized, placebo-controlled, double blind trial to study the effects of Etidronate on ectopic CALCIfication in FAhr*s Disease or syndrome.
- Conditions
- Fahr's diseaseprimary familial brain calcification10007963
- Registration Number
- NL-OMON53560
- Lead Sponsor
- niversitair Medisch Centrum Utrecht
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 98
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:
a. Clinical symptoms consistent with a clinical diagnosis of Fahr*s disease or
syndrome.
b. Bilateral calcifications of the basal ganglia as seen on the 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
Fahr's disease:
c. 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 Fahr*s disease is supportive for the clinical
diagnosis of Fahr*s disease.
d. The presence of a (likely) pathogenic mutation in one of the Fahr*s
disease-related genes is supportive for the clinical diagnosis of Fahr*s
disease. Mutations in up to now four known genes are associated with an
autosomal dominant pattern of inheritance: SLC20A2 (OMIM#213600), XPR1
(OMIM#616413), PDGFB (OMIM#615483), and PDGFRB (OMIM#615007). Autosomal
recessively inherited PFBC is associated with mutations in two genes: MYORG
(OMIM#618317) and JAM2 (OMIM#618824).
1. Unable or unwilling to sign an informed consent.
2. Severe renal impairment (estimated creatinine clearance/eGFR of <30
ml/min/1.73m2 calculated using CKD-EPI equation).
3. Contraindication to receiving oral medication.
4. Known abnormality of the esophagus that would interfere with the passage of
the drug.
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. Any other medical or social condition that, in the opinion of the Principal
Investigator, might put the subject at risk of harm during the study or might
adversely affect the interpretation of the study data.
8. Use of bisphosphonate during the last 5 years.
9. Hypocalcemia (calcium <2.20 mmol/L)*.
10. 25-OH vitamin D deficiency <35 nmol/L)*.
*After correcting the hypocalcemia or vitamin D deficiency, a participant is
again suitable for participation in the CALCIFADE trial, as long as the
participant meets the inclusion criteria.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary outcome: change in cognitive functioning of patients with Fahr*s<br /><br>disease or syndrome treated with etidronate or placebo between baseline and 12<br /><br>months after baseline.</p><br>
- Secondary Outcome Measures
Name Time Method <p>Secondary outcomes: change in mobility, psychiatric symptoms, daily<br /><br>functioning, quality of life, and calcification in the brain of patients with<br /><br>Fahr*s disease or syndrome treated with etidronate or placebo between baseline<br /><br>and 12 months after baseline. </p><br>