A randomized, placebo-controlled, double blind trial to study the effects of Etidronate on ectopic CALCIfication in FAhr’s Disease or syndrome: CALCIFADE trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universitair Medisch Centrum Utrecht

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Decision date (initial)

2024-10-03

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Hersenstiching

External identifiers

EU CT number

2024-512300-19-00

EudraCT number

2022-003299-17

ClinicalTrials.gov

NCT05662111

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

The primary objective is to determine whether etidronate can halt or attenuate deterioration of cognitive functioning in patients with Fahr’s disease or syndrome.

Secondary objectives 5

1. To determine whether etidronate can halt or attenuate deterioration of mobility in patients with Fahr’s disease or syndrome.
2. To determine whether etidronate can halt or attenuate deterioration of psychiatric problems in patients with Fahr’s disease or syndrome.
3. To determine whether etidronate can halt or attenuate deterioration of dependence in activities of daily living in patients with Fahr’s disease or syndrome.
4. To determine whether etidronate can halt or attenuate deterioration of quality of life in patients with Fahr’s disease or syndrome.
5. To determine whether etidronate leads to stabilization of attenuation of ongoing calcification in the brain as quantified by CT imaging in patients with Fahr’s disease or syndrome.

Conditions and MedDRA coding

Fahr's disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

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.
3. Supportive criteria for the clinical diagnosis of PFBC: 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 PFBC is supportive for the clinical diagnosis of PFBC. d. 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: 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).

Exclusion criteria 10

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 last 5 years.
9. Hypocalcemia (calcium <2,20 mmol/L) (After correcting the hypocalcemia, a participant is again suitable for participation in the CALCIFADE trial, as long as the participant meets the inclusion criteria.)
10. 25-OH vitamin D deficiency <35 nmol/L) (After correcting the vitamin D deficiency, a participant is again suitable for participation in the CALCIFADE trial, as long as the participant meets the inclusion criteria.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change in cognitive functioning of patients with Fahr’s disease or syndrome treated with etidronate or placebo between baseline and 12 months after baseline.

Secondary endpoints 5

1. Change in mobility of patients with Fahr’s disease or syndrome treated with etidronate or placebo between baseline and 12 months after baseline.
2. Change in psychiatric symptoms of patients with Fahr’s disease or syndrome treated with etidronate or placebo between baseline and 12 months after baseline.
3. Change in daily functioning of patients with Fahr’s disease or syndrome treated with etidronate or placebo between baseline and 12 months after baseline.
4. Change in quality of life of patients with Fahr’s disease or syndrome treated with etidronate or placebo between baseline and 12 months after baseline.
5. Change in calcification in the brain of patients with Fahr’s disease or syndrome treated with etidronate or placebo between baseline and 12 months after baseline.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitair Medisch Centrum Utrecht

Sponsor organisation

Universitair Medisch Centrum Utrecht

Address

Heidelberglaan 100

City

Utrecht

Postcode

3584 CX

Country

Netherlands

Scientific contact point

Organisation

Universitair Medisch Centrum Utrecht

Contact name

Birgitta Snijders

Public contact point

Organisation

Universitair Medisch Centrum Utrecht

Contact name

Birgitta Snijders

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications