Amantadine for Improving Neurologic Symptoms in Ataxia-Telangiectasia
キーワード
概要
説明
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.
日付
最終確認済み: | 05/31/2011 |
最初に提出された: | 07/29/2009 |
提出された推定登録数: | 07/29/2009 |
最初の投稿: | 07/30/2009 |
最終更新が送信されました: | 06/25/2011 |
最終更新日: | 06/27/2011 |
実際の研究開始日: | 10/31/2008 |
一次完了予定日: | 10/31/2009 |
研究完了予定日: | 10/31/2009 |
状態または病気
介入/治療
Drug: amantadine (PKMERZ)
段階
アームグループ
腕 | 介入/治療 |
---|---|
Experimental: amantadine (PKMERZ) | Drug: amantadine (PKMERZ) 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 |
適格基準
研究の対象となる年齢 | 4 Years に 4 Years |
研究に適格な性別 | All |
健康なボランティアを受け入れる | はい |
基準 | 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 |
結果
主な結果の測定
1. improvement in ataxia [2 month]
二次的な結果の測定
1. improvement in extrapyramidal movement disorder [2 month]