Lithium and Acetate for Canavan Disease

Condition(s) targeted: Canavan Disease; Infantile; Deficiency Disease; Aspartoacylase; Leukodystrophy, Spongiform

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

Phase: Phase 2

Status: Withdrawn

Sponsored by: Assistance Publique - Hôpitaux de Paris

Official(s) and/or principal investigator(s):
Patrick Aubourg, MD, PhD, Principal Investigator, Affiliation: Assistance Publique - Hôpitaux de Paris
Caroline Sevin, MD, PhD, Principal Investigator, Affiliation: Assistance Publique - Hôpitaux de Paris

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.

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

Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: 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.

Secondary outcome:

Secondary outcomes will be assessed at 10 months (end of the treatment): -Improvement of neuromotor performances (GMFM and Mullen scales), spasticity, and neurological severity

-Improvement of epilepsy (number of seizures)

-Decrease in NAA and increase in acetate contents in fluids (CSF, plasma, urine).

Detailed 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.

Minimum age: 1 Year. Maximum age: 15 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Clinical and biochemical diagnosis of Canavan disease

Exclusion Criteria:

- Renal disease

- Thyroid disease

- Cardiac disease

- Impossibility to perform brain MRI

ELA (European Leukodystrophy Association)

Starting date: September 2009
Last updated: April 20, 2015