Evaluation of a Treatment With Allopurinol on Autistic Disorders and Epilepsy in Adenylosuccinate Lyase Deficiency (ADSL)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 8
- 试验地点
- 2
- 主要终点
- Measurement of adaptive functional improvement : composite total score for Vineland II adaptive behaviour Scale
研究概览
简要总结
The aim of this study is to evaluate the effectiveness of allopurinol treatment at 12 months on the adaptive and cognitive functioning of patients with adenylosuccinate lyase deficiency (ADSL). The psychiatric evaluation will involve the use of standardized tools prior to initiation of treatment, and will be repeated 6 months and 12 months after the start of treatment.
The decrease in the concentration of SAICAR and S-Ado metabolites, which are markers of adenylosuccinate lyase (ADSL) deficiency, will also be quantified.
Similarly, the efficacy of allopurinol on epileptic seizures for epileptic patients and on electrocardiogram abnormalities will be evaluated secondarily
详细描述
Adenylosuccinate lyase deficiency (ADSL) is a rare disorder of purine metabolism whose symptoms are mental retardation, autistic disorders, epilepsy, related to the accumulation of succinylpurines: succinylaminoimidazole carboxamide riboside (SAICAr) and succinyladenosine (S- Ado). The S-Ado / SAICAr ratio in the cerebrospinal fluid (CSF) is correlated with the clinical severity: the cerebral toxicity of SAICAr is incriminated. There is no specific treatment.
Based on the work of Gertrude B. Elion (1988 Nobel Prize in Medicine), who reports that allopurinol (a structural analogue of hypoxanthine) can be a substrate for hypoxanthine phosphoribosyltransferase (HPRT) and thus produce allopurinol ribonucleotides with as a first step in the de novo synthesis of purines, investigators tested the hypothesis that treatment with allopurinol in children with ADSL deficiency would reduce the production of the toxic metabolite SAICAr.
This hypothesis was validated in 3 minor patients with biological and clinical improvement.
So the investigators put the phase II, non-comparative study based on 4 visits to Necker-Enfants malades Hospital or La Pitié-Salpêtrière Hospital: Month 0 (before treatment), Month 3, Month 6 and Month 12 after the start of treatment.
After verification of the inclusion criteria and information of the parents or the patient or guardian, signature of the consent and inclusion of the patient:
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Months 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Child (minimum age 18 months) or adult with adenylosuccinate lyase; deficiency (ADSL) confirmed by quantification of SAICAr and S-Ado urinary;
- •Girls / women of childbearing age must:
- •have a negative pregnancy test;
- •agree to use a reliable method of contraception from the baseline visit to the last dose of study treatment
- •Consent of the patient, his parents or his legal representative;
- •Beneficiary of social security (affiliated or entitled).
排除标准
- •Refusal of the child, his parents or the patient or his representative;
- •Allergy known to allopurinol or to one of the constituents of the product (lactose in particular);
- •Patients treated with Antipurines (azathioprine, mercaptopurine);
- •Patients treated with vidarabine, cytotoxic drugs (eg cyclophosphamide, doxorubicin, bleomycin, procarbazine, alkyl halides), ciclosporin, or didanosine
- •Renal failure characterized by creatinine clearance <80 ml/mn
- •Hepatic insufficiency
- •Medullary insufficiency but possibly serious
- •Breastfeeding
- •Pregnancy or wishing to conceive during the study period
研究组 & 干预措施
Allopurinol
Oral administration of Allopurinol (Zyloric®) for 12 months without exceeding 400 mg / day in children and 900 mg / day in adults, with dosage adjustment in case of renal failure
干预措施: Allopurinol (Drug)
结局指标
主要结局
Measurement of adaptive functional improvement : composite total score for Vineland II adaptive behaviour Scale
时间窗: 12 months
to assess Efficacy of Allopurinol (Zyloric)® treatment from Baseline : For each scale : Mean : 100 SD : 15 * Adaptive behaviour composite : Range 20 to 180 -Domains scores : Range 20 to 140 -Communication : Range 20 to 140 -Daily living skills : Range 20 to 140 -Socialization : 20 to 140 -Motor skills : 20 to 140 For each scale values are considered to be better or worse outcome :High 130 to 140 -Moderately High 115 to 129 -Adequate 86 to 114 -Moderately Low 71 to 85 -Low 20 to 70 Total score is obtained by summing the subdomains scores
次要结局
- Evolution of the Score ADI-R (Autism Diagnostic Interview-Revised) from baseline(at 0, 12 months)
- Evolution of the Score on ABC scale (Aberrant Behaviour Checklist)(at 0, 6 months and 12 months)
- Evolution of S-Ado levels in the blood(at 0, 6 months and 12 months)
- Evolution of antiepileptic treatments from Baseline for epileptic patients(at 0 and 12 months)
- Evolution of the Scores of different subdomains Vineland II scale from baseline(at 0, 6 months and 12 months)
- Evolution of the Psycho-Educative Profile (PEP III/R) from baseline(at 0, 12 months)
- Evolution of the Score ADOS-2 (Autism Diagnostic Observation Schedule 2) from baseline(at 0, 12 months)
- Evolution of SAICAr levels in the urine(at 0, 6 months and 12 months)
- Evolution of S-Ado levels in the urine(at 0, 6 months and 12 months)
- Evolution of SAICAr levels in the blood(at 0, 6 months and 12 months)
- Evolution of the number of seizures from Baseline for epileptic patients(at 0 and 12 months)
- Evolution of electroencephalogram tracing from Baseline for epileptic patients(at 0 and 12 months)
- Evolution of the Score on Conners hyperactivity Scale(at 0, 6 months and 12 months)