Amantadine for Improving Neurologic Symptoms in Ataxia-Telangiectasia
Condition: Ataxia; Chorea; Dystonia; Parkinsonism; Fatigue
MeSH terms: Ataxia; Cerebellar Ataxia; Dystonia; Parkinsonian Disorders; Ataxia Telangiectasia; Telangiectasis
Study type: Interventional
Phase: Phase 4

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.
    

Intervention name(s): amantadine sulphate
Intervention type(s): Drug
Intervention description(s): 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 intervention name(s): PKMERZ
Intervention MeSH terms: Amantadine
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment