Canavan DiseasePhase 2NCT00657748
Lithium and Acetate for Canavan Disease
A Phase 2 study testing Lithium Gluconate (drug) Glyceryl Triacetate GTA (drug) in people with Canavan Disease and Infantile, run by Assistance Publique - Hôpitaux de Paris.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 1 year to 15 years
- Conditions the study is for
- Canavan Disease, Infantile, Deficiency Disease
- What is being tested?
- Lithium Gluconate (drug) Glyceryl Triacetate GTA (drug)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Sep 2009to Jan 2011
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 15 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Clinical and biochemical diagnosis of Canavan disease
Who cannot join
- Renal disease
- Thyroid disease
- Cardiac disease
- Impossibility to perform brain MRI
About this study
Official title: Evaluation of the Tolerance and Efficiency of a Combined Oral Therapy With Lithium and GTA in Patients With Canavan Disease
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.
Read the 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.
- Conditions
- Canavan Disease, Infantile, Deficiency Disease, Aspartoacylase, Leukodystrophy, Spongiform
- Being tested
- Lithium Gluconate (drug) Glyceryl Triacetate GTA (drug)
- Keywords
- Leukodystrophy, Canavan disease,, Aspartoacylase,, Lithium,, Glyceryl Triacetate
- Medical subject headings
- Canavan Disease, Deficiency Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lithium Gluconate (drug) Glyceryl Triacetate GTA (drug)Drug
Also called Lithium Gluconate (drug), Glyceryl Triacetate, GTA (drug)
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
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Not described Receives: Drug: Lithium Gluconate (drug) Glyceryl Triacetate GTA (drug) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 10 months
Secondary outcomes (3)
Secondary outcomes will be assessed at 10 months (end of the treatment): -Improvement of neuromotor performances (GMFM and Mullen scales), spasticity, and neurological severity
Measured: 10 months
-Improvement of epilepsy (number of seizures)
Measured: 10 months
-Decrease in NAA and increase in acetate contents in fluids (CSF, plasma, urine).
Measured: 10 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Apr 2008 (estimated)
- Study startSep 2009
- Primary completionSep 2010
- Study completionJan 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Canavan DiseaseStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- European Leukodystrophy Association
- Investigators
- Patrick Aubourg, MD, PhD, Principal investigator, Assistance Publique - Hôpitaux de ParisCaroline Sevin, MD, PhD, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00657748
- Sponsor's protocol ID
- P070803
- Status last verified
- Apr 2015
- First submitted
- 9 Apr 2008
- Last updated
- 21 Apr 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Mathew R, Arun P, Madhavarao CN, Moffett JR, Namboodiri MA. Progress toward acetate supplementation therapy for Canavan disease: glyceryl triacetate administration increases acetate, but not N-acetylaspartate, levels in brain. J Pharmacol Exp Ther. 2005 Oct;315(1):297-303. doi: 10.1124/jpet.105.087536. Epub 2005 Jul 7.
PubMed 16002461Madhavarao CN, Arun P, Moffett JR, Szucs S, Surendran S, Matalon R, Garbern J, Hristova D, Johnson A, Jiang W, Namboodiri MA. Defective N-acetylaspartate catabolism reduces brain acetate levels and myelin lipid synthesis in Canavan's disease. Proc Natl Acad Sci U S A. 2005 Apr 5;102(14):5221-6. doi: 10.1073/pnas.0409184102. Epub 2005 Mar 22.
PubMed 15784740Janson CG, Assadi M, Francis J, Bilaniuk L, Shera D, Leone P. Lithium citrate for Canavan disease. Pediatr Neurol. 2005 Oct;33(4):235-43. doi: 10.1016/j.pediatrneurol.2005.04.015.
PubMed 16194720Baslow MH, Kitada K, Suckow RF, Hungund BL, Serikawa T. The effects of lithium chloride and other substances on levels of brain N-acetyl-L-aspartic acid in Canavan disease-like rats. Neurochem Res. 2002 May;27(5):403-6. doi: 10.1023/a:1015504031229.
PubMed 12064356
Study at a glance
From the registry record, last updated by the sponsor on 21 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Tolerance and Efficiency of a Combined Oral Therapy With Lithium and GTA in Patients With Canavan Disease
- ClinicalTrials.gov ID
- NCT00657748
- Acronym / sponsor ID
- P070803
- Conditions
- Canavan Disease, Infantile, Deficiency Disease, Aspartoacylase, Leukodystrophy, Spongiform
- Keywords
- Leukodystrophy, Canavan disease,, Aspartoacylase,, Lithium,, Glyceryl Triacetate
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- European Leukodystrophy Association
- Study start
- Sep 2009
- Primary completion
- Sep 2010 (actual)
- Study completion
- Jan 2011 (actual)
- First posted
- 14 Apr 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Lithium Gluconate (drug) Glyceryl Triacetate GTA (drug) |
Who may qualify
- Ages
- 1 year to 15 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (1 listed)
- Clinical and biochemical diagnosis of Canavan disease
Key exclusion criteria (4 listed)
- Renal disease
- Thyroid disease
- Cardiac disease
- Impossibility to perform brain MRI
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lithium Gluconate (drug) Glyceryl Triacetate GTA (drug)Also: Lithium Gluconate (drug), Glyceryl Triacetate, GTA (drug)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 | Drug | 1 |
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.
Time frame: 10 months
3 secondary outcomes
Secondary outcomes will be assessed at 10 months (end of the treatment): -Improvement of neuromotor performances (GMFM and Mullen scales), spasticity, and neurological severity
Time frame: 10 months
-Improvement of epilepsy (number of seizures)
Time frame: 10 months
-Decrease in NAA and increase in acetate contents in fluids (CSF, plasma, urine).
Time frame: 10 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Apr 2015.
- Results publication: PubMed 16002461Mathew R, Arun P, Madhavarao CN, Moffett JR, Namboodiri MA. Progress toward acetate supplementation therapy for Canavan disease: glyceryl triacetate administration increases acetate, but not N-acetylaspartate, levels in brain. J Pharmacol Exp Ther. 2005 Oct;315(1):297-303. doi: 10.1124/jpet.105.087536. Epub 2005 Jul 7.
- Results publication: PubMed 15784740Madhavarao CN, Arun P, Moffett JR, Szucs S, Surendran S, Matalon R, Garbern J, Hristova D, Johnson A, Jiang W, Namboodiri MA. Defective N-acetylaspartate catabolism reduces brain acetate levels and myelin lipid synthesis in Canavan's disease. Proc Natl Acad Sci U S A. 2005 Apr 5;102(14):5221-6. doi: 10.1073/pnas.0409184102. Epub 2005 Mar 22.
- Results publication: PubMed 16194720Janson CG, Assadi M, Francis J, Bilaniuk L, Shera D, Leone P. Lithium citrate for Canavan disease. Pediatr Neurol. 2005 Oct;33(4):235-43. doi: 10.1016/j.pediatrneurol.2005.04.015.
- Results publication: PubMed 12064356Baslow MH, Kitada K, Suckow RF, Hungund BL, Serikawa T. The effects of lithium chloride and other substances on levels of brain N-acetyl-L-aspartic acid in Canavan disease-like rats. Neurochem Res. 2002 May;27(5):403-6. doi: 10.1023/a:1015504031229.
- ELA (European Leukodystrophy Association)Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Patrick Aubourg, MD, PhD principal investigator
Assistance Publique - Hôpitaux de Paris
Caroline Sevin, MD, PhD principal investigator
Assistance Publique - Hôpitaux de Paris
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Lithium Gluconate (drug) Glyceryl Triacetate GTA (drug) in people with Canavan Disease and Infantile, run by Assistance Publique - Hôpitaux de Paris.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 21 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. (time frame: 10 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00657748, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Apr 2015.