Evaluation of a Treatment With Allopurinol in Adenylosuccinate Lyase Deficiency

NCT03776656 | Completed Phase 2

• 2 other identifiers: P160902J2017-002155-28
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 2

Brief Summary

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

Conditions

Adenylosuccinate Lyase Deficiency

Keywords

Adenylosuccinate lyase; Deficit; Allopurinol; Autism; Epilepsy

Outcome Measures

Primary Outcomes (1)

• Measurement of adaptive functional improvement : composite total score for Vineland II adaptive behaviour Scale

  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

  12 months

Secondary Outcomes (13)

• 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 ADI-R (Autism Diagnostic Interview-Revised) 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 the Score on Conners hyperactivity Scale

  at 0, 6 months and 12 months

Study Arms (1)

Allopurinol

EXPERIMENTAL

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

Interventions

Allopurinol DRUG

Daily oral administration

Also known as: Zyloric®

Allopurinol

Eligibility Criteria

• Age: 18 Months+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• URC-CIC Paris Descartes Necker Cochin: collaborator
• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (2)

LA PITIE-SALPETRIERE Hospital, AP-HP

Paris, 75013, France

Location

Department of Pediatry. Reference centre of Hereditary diseases of the metabolism of child and adult. Necker - Enfants malades Hospital

Paris, 75015, France

Location

Related Publications (1)

• Rousselot-Pailley B, Semeraro M, Marquant F, Robel L, Gitiaux C, Kaminska A, Mochel F, Bakouboula P, Elie C, Hennequin C, Ceballos-Picot I, Sanquer S, de Lonlay P. Allopurinol Treatment Improves Cognitive Skills, Adaptive Behavior, and Biochemical Markers in Young Patients With Adenylosuccinate Lyase Deficiency. J Inherit Metab Dis. 2025 Nov;48(6):e70092. doi: 10.1002/jimd.70092.

  PMID: 41053929 RESULT

MeSH Terms

Conditions

Adenylosuccinate lyase deficiency; Autistic Disorder; Epilepsy

Interventions

Allopurinol

Condition Hierarchy (Ancestors)

Autism Spectrum Disorder; Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Pascale De LONLAY, MD, PhD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

• Irène CEBALLOS-PICOT, MD, PhD

  Assistance Publique - Hôpitaux de Paris

  STUDY DIRECTOR

• Laurence ROBEL-GALLI, MD

  Assistance Publique - Hôpitaux de Paris

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 13, 2018
• First Posted: December 17, 2018
• Study Start: October 14, 2019
• Primary Completion: June 17, 2022
• Study Completion: June 17, 2022
• Last Updated: March 4, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

FR (2)