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Adenylosuccinate Lyase DeficiencyPhase 2ADSLNCT03776656

Evaluation of a Treatment With Allopurinol in Adenylosuccinate Lyase Deficiency

A Phase 2 study testing Allopurinol in people with Adenylosuccinate Lyase Deficiency, run by Assistance Publique - Hôpitaux de Paris at 2 sites in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 months and older
Conditions the study is for
Adenylosuccinate Lyase Deficiency
What is being tested?
Allopurinol
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
8 participants
Where
2 sitesFrance
Study dates
14 Oct 2019to 17 Jun 2022
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 months and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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).

Who cannot join

  • 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
Show all 9Show fewer
  • Medullary insufficiency but possibly serious
  • Breastfeeding
  • Pregnancy or wishing to conceive during the study period

Trial locations and contacts

2 sites in 1 country.

France2 sites

  • LA PITIE-SALPETRIERE Hospital, AP-HP

    Paris, 75013

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

    Paris, 75015

Other trials in France

About this study

Official title: Evaluation of a Treatment With Allopurinol on Autistic Disorders and Epilepsy in Adenylosuccinate Lyase Deficiency (ADSL)

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

Read the detailed description

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.
Being tested
Allopurinol
Keywords
Adenylosuccinate lyase, Deficit, Allopurinol, Autism, Epilepsy
Medical subject headings
Adenylosuccinate lyase deficiency, Autistic Disorder, Epilepsy

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AllopurinolDrug

    Also called Zyloric®

    Daily oral administration

Study groups in NCT03776656
Study groupRoleWhat they receive
AllopurinolExperimentalOral 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
Receives: Drug: Allopurinol

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 12 months

Secondary outcomes (13)

  1. Evolution of the Scores of different subdomains Vineland II scale from baseline

    Clinical evolution for developmental and cognitive assessment

    Measured: at 0, 6 months and 12 months

  2. Evolution of the Psycho-Educative Profile (PEP III/R) from baseline

    Clinical evolution for developmental and cognitive assessment

    Measured: at 0, 12 months

  3. Evolution of the Score ADI-R (Autism Diagnostic Interview-Revised) from baseline

    Clinical evaluation for autistic symptoms : scale ranges :

    • A : Social interactions: 0 to 30 (significative if >10)
    • B : Communication : 0 to 26 (significative if > 7 or 8)
    • C : Repetitive and restricted interests : 0 to 16 (significative if >3)
    • D : Developmental abnormality present before 36 months : 0 to 5 (significative if >1) better score : 0 (non autistic) - worse score : the higher score is the worst

    Measured: at 0, 12 months

  4. Evolution of the Score ADOS-2 (Autism Diagnostic Observation Schedule 2) from baseline

    Clinical evaluation for autistic symptoms. Scale ranges :

    • A : Socialization : social interactions and communication : 0 to 20 (social interactions : 0 to 6 -communication : 0 to 14)
    • B : Restricted and repetitive interests : 0 to 8
    • Total : A+B : 0 to 28

    Autism : total score>12 - Autism Spectrum Disorder : total score >8

    Better score : 0 - Worse score : the highest score is the worst

    Measured: at 0, 12 months

  5. Evolution of the Score on Conners hyperactivity Scale

    Clinical evolution for behavioral disorders and adaptive functioning

    Conners Scale for Parents :

    • Subscales : Behavioural difficulties (items 2-8-14-19-20-27-35-39) : 0 to 24 Learning difficulties (items 10-25-31-37) : 0 to 12 Somatisation (items 32-41-43-44) : 0 to 12 Impulsivity, hyperactivity (items 4-5-11-13): 0 to 12 Anxiety (items 12-16-24-47): 0 to 12

    -Hyperactivity index : sum of the items (4-7-11-13-14-25-31-33-37-38) divided by 10 : 0 to 3

    Conners Scale for teachers :

    • Subscales : Behavioural difficulties (items 4-5-6-10-11-12-23-27) : 0 to 24 Impulsivity, hyperactivity (items 1-2-3-8-14-15-16) : 0 to 21 Inattention, passivity (items 7-9-18-20-21-22-26-28) : 0 to 24

    -Hyperactivity index (sum of the items 1-5-7-8-10-11-14-15-21-26 divided by 10) : 0 to 3

    Better score : 0 - Worse score : the highest score is the worst -Hyperactivity index : Significative if> 1,5

    Measured: at 0, 6 months and 12 months

  6. Evolution of the Score on ABC scale (Aberrant Behaviour Checklist)

    Clinical evolution for behavioral disorders and adaptive functioning scale ranges :

    • Irritability : 0 to 45
    • Lethargy : 0 to 48
    • Stereotypy : 0 to 21
    • Hyperactivity : 0 to 48
    • Inappropriate speech : 0 to 12

    Better score : 0 -Worse score : the highest score is the worst on each scale- there is no total score

    Measured: at 0, 6 months and 12 months

  7. Evolution of SAICAr levels in the urine

    Evolution of the quantity of urinary metabolites from Baseline

    Measured: at 0, 6 months and 12 months

  8. Evolution of S-Ado levels in the urine

    Evolution of the quantity of urinary metabolites from Baseline

    Measured: at 0, 6 months and 12 months

  9. Evolution of SAICAr levels in the blood

    Evolution of the quantity of plasma metabolites from Baseline

    Measured: at 0, 6 months and 12 months

  10. Evolution of S-Ado levels in the blood

    Evolution of the quantity of plasma metabolites from Baseline

    Measured: at 0, 6 months and 12 months

  11. Evolution of the number of seizures from Baseline for epileptic patients

    at baseline, performing neurological examinations and interrogation

    Measured: at 0 and 12 months

  12. Evolution of antiepileptic treatments from Baseline for epileptic patients

    at baseline, performing neurological examinations and interrogation

    Measured: at 0 and 12 months

  13. Evolution of electroencephalogram tracing from Baseline for epileptic patients

    normal/abnormal

    Measured: at 0 and 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Dec 2018
  2. Study start14 Oct 2019
  3. Primary completion17 Jun 2022
  4. Study completion17 Jun 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
8 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03776656
Sponsor's protocol ID
P160902J
Other IDs
2017-002155-28, 2017
Acronym
ADSL
Status last verified
Feb 2026
First submitted
13 Aug 2018
Last updated
4 Mar 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 41053929

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Allopurinol in people with Adenylosuccinate Lyase Deficiency, run by Assistance Publique - Hôpitaux de Paris at 2 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Measurement of adaptive functional improvement : composite total score for Vineland II adaptive behaviour Scale (time frame: 12 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03776656, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2026.

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