Evaluation of a Treatment With Allopurinol in Adenylosuccinate Lyase Deficiency
কীওয়ার্ডস
বিমূর্ত
বর্ণনা
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:
- Clinical and neurological evaluation;
- Psychiatric assessment with standardized tests;
- Biological evaluation: determination of urinary and plasma metabolites (SAICAr, S-Ado, ...) Experimental treatment: Allopurinol (Zyloric®) will be administered orally for 12 months without exceeding 400 mg / day in children and 900 mg / day in adults, with dosage adjustment in case of renal failure.
তারিখ
| সর্বশেষ যাচাই করা হয়েছে: | 01/31/2019 |
| প্রথম জমা দেওয়া: | 08/12/2018 |
| আনুমানিক তালিকাভুক্তি জমা দেওয়া হয়েছে: | 12/11/2018 |
| প্রথম পোস্ট: | 12/16/2018 |
| সর্বশেষ আপডেট জমা দেওয়া হয়েছে: | 02/17/2019 |
| সর্বশেষ আপডেট পোস্ট: | 02/19/2019 |
| আসল অধ্যয়ন শুরুর তারিখ: | 04/30/2019 |
| আনুমানিক প্রাথমিক সমাপ্তির তারিখ: | 04/30/2021 |
| আনুমানিক অধ্যয়ন সমাপ্তির তারিখ: | 10/31/2021 |
অবস্থা বা রোগ
হস্তক্ষেপ / চিকিত্সা
Drug: Allopurinol
পর্যায়
বাহু গ্রুপ
| বাহু | হস্তক্ষেপ / চিকিত্সা |
|---|---|
| Experimental: 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 | Drug: Allopurinol Daily oral administration |
যোগ্যতার মানদণ্ড
| বয়স অধ্যয়নের জন্য যোগ্য | 18 Months প্রতি 18 Months |
| লিঙ্গ অধ্যয়নের জন্য যোগ্য | All |
| স্বাস্থ্যকর স্বেচ্ছাসেবীদের গ্রহণ করে | হ্যাঁ |
| নির্ণায়ক | Inclusion Criteria: - 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). Exclusion Criteria: - 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 |
ফলাফল
প্রাথমিক ফলাফল ব্যবস্থা
1. Measurement of adaptive functional improvement : composite total score for Vineland II adaptive behaviour Scale [12 months]
মাধ্যমিক ফলাফলের ব্যবস্থা
1. Evolution of the Scores of different subdomains Vineland II scale from baseline [at 0, 6 months and 12 months]
2. Evolution of the Psycho-Educative Profile (PEP III/R) from baseline [at 0, 12 months]
3. Evolution of the Score ADI-R (Autism Diagnostic Interview-Revised) from baseline [at 0, 12 months]
4. Evolution of the Score ADOS-2 (Autism Diagnostic Observation Schedule 2) from baseline [at 0, 12 months]
5. Evolution of the Score on Conners hyperactivity Scale [at 0, 6 months and 12 months]
6. Evolution of the Score on ABC scale (Aberrant Behaviour Checklist) [at 0, 6 months and 12 months]
7. Evolution of SAICAr levels in the urine [at 0, 6 months and 12 months]
8. Evolution of S-Ado levels in the urine [at 0, 6 months and 12 months]
9. Evolution of SAICAr levels in the blood [at 0, 6 months and 12 months]
10. Evolution of S-Ado levels in the blood [at 0, 6 months and 12 months]
11. Evolution of the number of seizures from Baseline for epileptic patients [at 0 and 12 months]
12. Evolution of antiepileptic treatments from Baseline for epileptic patients [at 0 and 12 months]
13. Evolution of electroencephalogram tracing from Baseline for epileptic patients [at 0 and 12 months]
