Lithium and Acetate for Canavan Disease

Assistance Publique - Hôpitaux de Paris

Status and phase: Withdrawn; Phase 2

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

Treatments: Drug: Lithium Gluconate (drug) Glyceryl Triacetate GTA (drug)

Study type: Interventional

Funder types: Other

Identifiers

NCT00657748

P070803

Details and patient eligibility

About

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.

Full description

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.

Sex: All

Ages: 1 to 15 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Clinical and biochemical diagnosis of Canavan disease

Exclusion criteria

• Renal disease
• Thyroid disease
• Cardiac disease
• Impossibility to perform brain MRI

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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0 participants in 1 patient group

1

Experimental group

Treatment:

Drug: Lithium Gluconate (drug) Glyceryl Triacetate GTA (drug)