Lithium and Acetate for Canavan Disease

Study Overview
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Brief Summary
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The aim of this study is to determine whether oral supplementation with lithium and acetate may improve the biological and clinical prognosis in patients with Canavan Disease.

Detailed Description
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Canavan Disease is an autosomal recessive devastating demyelinating disease caused by a deficiency in Aspartoacylase (ASPA) enzyme. There is no available treatment. ASPA deficiency leads to:- the accumulation of high levels of N-acetylaspartate (NAA), involved in myelin degeneration and epilepsy;- the deficient synthesis of acetate in oligodendrocytes, that could impair CNS myelination.Lithium administration induces a decrease in NAA in the brain of the tremor rats (animal model for CD) and in one patient (JANSON, 2005). On the other hand, administration of acetate could improve myelination in Canavan patients.For this reason, we propose to combine both treatments: Lithium Gluconate and Glyceryl Triacetate (GTA). Eighteen patients, aged 1 to 15 years, will receive oral GTA or Lithium during 4 months, then both treatment in association during 6 months. Patients will be sequentially evaluated up to the end of the treatment and 2 months thereafter for:-tolerance of the therapy (careful monitoring of clinical and biological parameters).- efficacy of the therapy on clinical, biological and radiological parameters. Particularly, we will evaluate using MRI-spectroscopy and CSF samples the decrease in NAA and increase in acetate levels in the brain.

Official Title
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Evaluation of the Tolerance and Efficiency of a Combined Oral Therapy With Lithium and GTA in Patients With Canavan Disease

Conditions
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Canavan Disease, Infantile, Deficiency Disease, Aspartoacylase, Leukodystrophy, Spongiform

Intervention / Treatment
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* Drug: Lithium Gluconate (drug) Glyceryl Triacetate GTA (drug)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical and biochemical diagnosis of Canavan disease Exclusion Criteria: Renal disease Thyroid disease Cardiac disease Impossibility to perform brain MRI

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 15 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: Lithium Gluconate (drug) Glyceryl Triacetate GTA (drug)<br>* Lithium 1.3 mEq/kg/day (three administrations a day)during the study GTA 500 mg/kg/day in four administrations a day during the study<br>* Other names: Glyceryl Triacetate, GTA (drug);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary outcome will be a decrease of the NAA peak (> 20%) or the appearance of an acetate peak at the end of the treatment (10 months), using spectroscopy-MRI. |  | 10 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary outcomes will be assessed at 10 months (end of the treatment): -Improvement of neuromotor performances (GMFM and Mullen scales), spasticity, and neurological severity |  | 10 months | 
| -Improvement of epilepsy (number of seizures) |  | 10 months | 
| -Decrease in NAA and increase in acetate contents in fluids (CSF, plasma, urine). |  | 10 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Leukodystrophy, Canavan disease,, Aspartoacylase,, Lithium,, Glyceryl Triacetate