Amantadine for Improving Neurologic Symptoms in Ataxia-Telangiectasia

This study has been completed.
Sponsor:
Information provided by:
Sheba Medical Center
ClinicalTrials.gov Identifier:
NCT00950196
First received: July 30, 2009
Last updated: June 26, 2011
Last verified: June 2011
  Purpose

Ataxia-Telangiectasia A-T is a neurodegenerative disorder of the cerebellum, manifesting with ataxia, as well as extrapyramidal features. Treatment of A-T is discouraging, since no treatment seems to change the course of disease, but improvement can be achieved by symptomatic treatment of the bothersome movement disorder . While various dopaminergic agents are occasionally used, reports of benefit are rather sparse and anecdotal. Amantadine, a well known drug used in influenza as well as movement disorder of Parkinson, has been proved to improve various other types of movement disorder as ataxia, chorea, dystonia, akinesia and attention span. The purpose of this study is to investigate weather amantadine sulphate improves ataxia and the movement disorder (bradykinesia, parkinsonism, dystonia, chorea), as well as the general well being in patients with A-T.


Condition Intervention Phase
Ataxia
Chorea
Dystonia
Parkinsonism
Fatigue
Drug: amantadine sulphate
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: The Effect of Amantadine on Movement Disorder in Ataxia-Telangiectasia

Resource links provided by NLM:


Further study details as provided by Sheba Medical Center:

Primary Outcome Measures:
  • improvement in ataxia [ Time Frame: 2 month ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • improvement in extrapyramidal movement disorder [ Time Frame: 2 month ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: November 2008
Study Completion Date: November 2009
Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: amantadine (PKMERZ) Drug: amantadine sulphate
amantadine 5/mg/kg for 2 month- tapered up during 2 weeks at 1 month possibility to increase dosage to 8 mg/kg or reduce it if there are side effects
Other Name: PKMERZ

Detailed Description:

Ataxia-Telangiectasia (A-T) is a complex multisystem disorder with neurodegenerative course, immune deficiency, and tendency to develop malignancies .The clinical picture includes progressive cerebellar ataxia along with a movement disorder (chorea, dystonia or bradykinesia) that may be even more disabling than the ataxia . Fatigability, drooling and reduced stamina are other major concerns. Disease course is devastating: towards the second decade of life the affected children are usually bound to wheelchair and survival beyond the second decade of life is rare. Treatment of A-T is discouraging, since no treatment seems to change the course of disease, but improvement can be achieved by symptomatic treatment of the bothersome movement disorder . While various dopaminergic agents are occasionally used, reports of benefit are rather sparse and anecdotal.

Amantadine is a dopaminergic agent approved for prophylaxis of influenza (in children over 1 year of age and adults) as well as for extrapyramidal disorders in adults: Parkinson disease and drug induced dyskinesias . Amantadine increases dopaminergic transmission by inhibiting its synaptic uptake, as well as an antagonizing the striatal NMDA receptors). Additional conditions found to be improved with amantadine are: cerebellar ataxia, vigilance after brain trauma in adults and children ,attention deficit disorder in children, chorea and akinesia in Huntington's disease .

Amantadine is an FDA approved drug for treatment and prevention of influenza, Parkinson disease and drug induced dyskinesia; it is approved for use in adults and children over 1 year of age.

Dosage in children: 5 mg/kg body weight up to 8.8mg/kg/. Dosage in adults: 200 to 300 mg/day. The daily dosage should be divided into 2 to 3 daily portions. Amantadine is a safe drug with mild side effects: headache, decreased appetite, sedation, fatigue, abdominal pain, vomiting, insomnia, pedal edema and rash (4-10).

Studies in children proved amantadine to be a safe and tolerable drug. Amantadine was administered to 24 healthy children with ADHD, aged 5-13 year old . Side effects were present in 13/24 and were usually mild: decreased appetite, headache, sedation, mild insomnia, vomiting, fatigue, abdominal pain. One subject dropped out because of headache. Six low response children after traumatic brain injury were treated with amantadine (concurrently with other medication) The drug was safe with relatively mild side effects: sedation, intermittent tremor, dizziness, but no serious side effects requiring discontinuation of the protocol.

Study purpose The purpose of this study is to investigate weather amantadine sulphate improves ataxia and the movement disorder (bradykinesia, parkinsonism, dystonia, chorea), as well as the general well being in patients with A-T.

  Eligibility

Ages Eligible for Study:   4 Years to 50 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • diagnosis of A-T
  • significant functional disability
  • age over 4 years

Exclusion Criteria:

  • major comorbidity: active malignancy requiring chemotherapy, kidney or liver failure
  • sexually active
  • known hypersensitivity to amantadine
  • previous treatment with amantadine in the 2 months preceding the study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00950196

Locations
Israel
Sheba Medical Center
Ramat Gan, Israel
Sponsors and Collaborators
Sheba Medical Center
Investigators
Principal Investigator: Andreea Nissenkorn, MD Sheba Medical Center, Pediatric Neurology and National A-T Clinic
  More Information

No publications provided by Sheba Medical Center

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Andreea Nissenkorn, MD, Pediatric Neurologist, Director National A-T Clinic, Sheba Medical Center
ClinicalTrials.gov Identifier: NCT00950196     History of Changes
Other Study ID Numbers: SHEBA-08-5196-AN-CTIL
Study First Received: July 30, 2009
Last Updated: June 26, 2011
Health Authority: Israel: Israeli Health Ministry Pharmaceutical Administration

Additional relevant MeSH terms:
Telangiectasis
Ataxia
Parkinsonian Disorders
Ataxia Telangiectasia
Vascular Diseases
Cardiovascular Diseases
Dyskinesias
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Movement Disorders
Spinocerebellar Ataxias
Cerebellar Ataxia
Cerebellar Diseases
Neurocutaneous Syndromes
Genetic Diseases, Inborn
DNA Repair-Deficiency Disorders
Metabolic Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Amantadine
Antiparkinson Agents
Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Antiviral Agents

ClinicalTrials.gov processed this record on October 01, 2014