Health TrialsbyHealthPanel

Treatment of Ectopic Calcification in Fahr's Disease or Syndrome

ConditionsFahr DiseaseFahr SyndromePrimary Familial Brain Calcification
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorUMC Utrecht

About this trial

Fahr's disease or syndrome are neurodegenerative diseases in which patients present with bilateral vessel associated calcifications in the basal ganglia. The clinical penetration of Fahr's disease or syndrome is incomplete and heterogeneous comprising of neuropsychiatric signs, cognitive decline, movement disorders, and various other signs (migraine, speech disorders, pain, seizures). The symptoms start between 30 and 50 years and are (slowly) progressive. Symptomatic patients have an increased risk for dependence in activities of daily living and impaired quality of life.

Currently, disease-modifying therapies are not available for patients with Fahr's disease or syndrome. However, in a small case series it was shown that alendronate was effective in the clinical treatment of several patients with Fahr's disease or syndrome. Now the time has come to investigate the effectiveness of treatment with bisphosphonates in patients with Fahr's disease or syndrome in a randomized controlled trial.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Age of 18 years or over,

Clinical symptoms consistent with a clinical diagnosis of Fahr's disease or syndrome.

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.

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.

Disqualifiers

unable or unwilling to sign an informed consent,

severe renal impairment (estimated glomerular filtration rate (eGFR) of <30 ml/min/1.73m2 calculated using CKD-EPI equation),

contraindication to receiving oral medication (for example severe dysphagia),

known abnormality of the oesophagus that would interfere with the passage of the drug (for example oesophageal strictures or achalasia),

Trial design

Design model

Parallel

Treatments tested in this trial

  • Etidronate

    Drug

    The dosage of etidronate is 20 mg/kg for twee weeks and ten weeks off. Etidronate is given in capsules of 200 mg. Etidronate capsules are administered orally. During the study, participants will receive etidronate in four periods of two weeks during the twelve months of follow-up.

  • Placebo

    Drug

    Placebo is given in capsules and are administered orally. During the study, participants will receive placebo in four periods of two weeks during the twelve months of follow-up.

Treatment groups

98 Participants
are divided into 2 treatment groups
Group A: EtidronateActive comparator 1 intervention
Group B: PlaceboPlacebo comparator 1 intervention

Trial outcomes

Primary outcomes

1

Overall cognitive functioning

Montreal Cognitive Assessment (MoCA; range 0-30, higher scores mean better outcome)

Time frame
12 months
2

Memory

Composite z-score of Rivermead Behavioral Memory Test (RBMT) Stories immediate and delayed recall, Rey complex figure test immediate and delayed recall

Time frame
12 months
3

Attention and speed of information processing

Composite z-score of Wechsler Adult Intelligence Scale third edition (WAIS-III) Digit Span Forward, Trail Making Test A (TMT-A), Stroop I and II

Time frame
12 months
4

Executive functioning

Composite z-score of Wechsler Adult Intelligence Scale third edition (WAIS-III) Digit Span Backward, Trail Making Test B (TMT-B), Stroop III, semantic and letter fluency

Time frame
12 months

Secondary outcomes

1

Mobility

Condensed version of the Balance Evaluation Systems Test (Mini-BESTest), which is a composite test of gait and balance (range 0-28, higher scores mean better outcome)

Time frame
12 months
2

Mobility

Unified Parkinson's Disease Rating Scale, part III (UPDRS; range 0-56, higher scores mean worse outcome)

Time frame
12 months
3

Neuropsychiatric symptoms

Neuropsychiatric Inventory (NPI; range 0-144, higher scores mean worse outcome)

Time frame
12 months
4

Activities of daily living

Katz-15 scale (range 0-15, higher scores mean worse outcome)

Time frame
12 months

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

UMC Utrecht

Lead sponsor

Netherlands Brain Foundation

Collaborator

Source ClinicalTrials.gov
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