Betaine METABOLISM OF PATIENTS With Homocystinuria

NCT02404337 — Phase 2, Completed, 12 participants, Assistance Publique - Hôpitaux de Paris

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Registry	NCT02404337, acronym HCTBETAINE
Status	Completed
Phase	Phase 2
Study type	Interventional; randomized, crossover, masking: none, treatment
Enrollment	12 (Actual)
Sponsor	Assistance Publique - Hôpitaux de Paris (Other)
Conditions	Homocystinuria
Interventions	Betaine (Drug)
Dates	start 2015-07-01, primary completion 2017-12-01, completion 2018-02-01, first posted 2015-03-31, last updated 2023-02-03
Locations	1 site in France

-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.

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+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.

+Arms and interventions

Arm	Type	Interventions	Description
100 mg/kg of Betaine	Experimental	Drug: Betaine	Dose 1 : 100 mg/kg of Betaine
250 mg/kg of Betaine	Experimental	Drug: Betaine	Dose 2 : 250 mg/kg of Betaine

Betaine (Drug)

+Outcome measures

Primary outcomes

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 outcomes

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]

+Eligibility

Sex: All, ages: 1 Year to 18 Years

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

+Locations (1)

Facility	City	Country	Status
Assistance Publique - Hôpitaux de Paris	Paris	France

+Publications

Results publication: Imbard A, Toumazi A, Magreault S, Garcia-Segarra N, Schlemmer D, Kaguelidou F, Perronneau I, Haignere J, de Baulny HO, Kuster A, Feillet F, Alberti C, Guilmin-Crepon S, Benoist JF, Schiff M. Efficacy and pharmacokinetics of betaine in CBS and cblC deficiencies: a cross-over randomized controlled trial. Orphanet J Rare Dis. 2022 Nov 14;17(1):417. doi: 10.1186/s13023-022-02567-4. PMID 36376887

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