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Amantadine for Improving Neurologic Symptoms in Ataxia-Telangiectasia

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ClinicalTrials.gov Identifier: NCT00950196
Recruitment Status : Completed
First Posted : July 31, 2009
Last Update Posted : June 28, 2011
Sponsor:
Information provided by:
Sheba Medical Center

Tracking Information
First Submitted Date  ICMJE July 30, 2009
First Posted Date  ICMJE July 31, 2009
Last Update Posted Date June 28, 2011
Study Start Date  ICMJE November 2008
Actual Primary Completion Date November 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 30, 2009)
improvement in ataxia [ Time Frame: 2 month ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT00950196 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 30, 2009)
improvement in extrapyramidal movement disorder [ Time Frame: 2 month ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Amantadine for Improving Neurologic Symptoms in Ataxia-Telangiectasia
Official Title  ICMJE The Effect of Amantadine on Movement Disorder in Ataxia-Telangiectasia
Brief Summary 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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Ataxia
  • Chorea
  • Dystonia
  • Parkinsonism
  • Fatigue
Intervention  ICMJE 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
Study Arms  ICMJE Experimental: amantadine (PKMERZ)
Intervention: Drug: amantadine sulphate
Publications * Nissenkorn A, Hassin-Baer S, Lerman SF, Levi YB, Tzadok M, Ben-Zeev B. Movement disorder in ataxia-telangiectasia: treatment with amantadine sulfate. J Child Neurol. 2013 Feb;28(2):155-60. doi: 10.1177/0883073812441999. Epub 2012 May 1.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Estimated Enrollment  ICMJE
 (submitted: July 30, 2009)
30
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE November 2009
Actual Primary Completion Date November 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 4 Years to 50 Months   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Israel
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00950196
Other Study ID Numbers  ICMJE SHEBA-08-5196-AN-CTIL
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Andreea Nissenkorn, MD, Pediatric Neurologist, Director National A-T Clinic, Sheba Medical Center
Study Sponsor  ICMJE Sheba Medical Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Andreea Nissenkorn, MD Sheba Medical Center, Pediatric Neurology and National A-T Clinic
PRS Account Sheba Medical Center
Verification Date June 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP