Betaine METABOLISM OF PATIENTS With Homocystinuria

Phase 2

Completed

• Conditions: Homocystinuria
• Interventions: Drug: Betaine

• Registration Number: NCT02404337
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

Oral treatment with betaine is conventionally used for patients with inherited homocystinurias.

These conditions include a first group of patients with a cystathionine β-synthase (CBS) deficiency and a second group of patients with remethylation defects.

The aim of betaine therapy is to reduce level of total plasma homocysteine. Daily dosages and rhythm of administration proposed in the literature vary between 100 to 250 mg / kg / d in 2 to 4 doses. These dosages are not based on validated data and several publications mention much higher dosages particularly when total homocysteine is not controlled. These practices may be unnecessary or even detrimental given the fact that high doses of betaine could for example lead to secondary folate deficiency.

Detailed Description

Oral treatment with betaine is conventionally used for patients with inherited homocystinurias.

These conditions include a first group of patients with a cystathionine β-synthase (CBS) deficiency and a second group of patients with remethylation defects.

The aim of betaine therapy is to reduce level of total plasma homocysteine. Daily dosages and rhythm of administration proposed in the literature vary between 100 to 250 mg / kg / d in 2 to 4 doses. These dosages are not based on validated data and several publications mention much higher dosages particularly when total homocysteine is not controlled. These practices may be unnecessary or even detrimental given the fact that high doses of betaine could for example lead to secondary folate deficiency.

Study Timeline

• Study First Submitted: 2015-03-06
• Study First Submitted QC: 2015-03-26
• Study First Posted: 2015-03-31
• Study Start: 2015-07
• Primary Completion: 2017-12
• Status Verified: 2018-02
• Study Completion: 2018-02
• Last Update Submitted: 2023-02-01
• Last Update Posted: 2023-02-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 12

Inclusion Criteria

• ≥1 year and children <18 years,

• homocystinuria confirmed enzymatically or molecularly divided into 2 groups:

  • CBS deficiency remethylation defects (CbIC defect and MTHFR deficiency)

• Diagnosis of homocystinuria since more than 1 year

• Continuous treatment of hyperhomocysteinemia in the last 12 months

Exclusion Criteria

• Deficits in cystathionine beta-synthase B6-responsive
• pregnancy
• breast-feeding
• Young pubescent girls not using effective contraception

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
250 mg/kg of Betaine	Betaine	Dose 2 : 250 mg/kg of Betaine
100 mg/kg of Betaine	Betaine	Dose 1 : 100 mg/kg of Betaine

Primary Outcome Measures

Name	Time	Method
Plasma level of total homocysteine upon oral treatment with Betaine at 100 mg / kg / day compared with 250 mg / kg / day in the same individual.	10 weeks - at the end of follow-up of each patient	The assay technique used is MS/MS validated according to ISO standard 1589. Samples will be frozen and analysed at the end of follow-up of the study. Freezing does not affect the validity of the technique used.

Secondary Outcome Measures

Name	Time	Method
Measurement of dimethylglycine plasma level following the loading dose of 100 mg / kg of betaine compared in the same person with the dose of 250 mg / kg.	10 weeks - at the end of follow-up of each patient
Measurement of sarcosine plasma level following the loading dose of 100 mg / kg of betaine compared in the same person with the dose of 250 mg / kg.	10 weeks - at the end of follow-up of each patient

Trial Locations

Locations (1)

Assistance Publique - Hôpitaux de Paris; 🇫🇷 Paris, France