Clinical trial NCT02404337: Betaine METABOLISM OF PATIENTS With Homocystinuria
Official title: Betaine METABOLISM OF PATIENTS With Homocystinuria
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Homocystinuria
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2015-03-31
Enrollment: 12
Sex: ALL
Minimum age (years): 1
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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.
timeFrame: 10 weeks - at the end of follow-up of each patient
Secondary outcomes:
measure: 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.
timeFrame: 10 weeks - at the end of follow-up of each patient
measure: 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.
timeFrame: 10 weeks - at the end of follow-up of each patient
Other outcomes:
Locations:
city: Paris
country: France
facility: Assistance Publique - Hôpitaux de Paris
Study officials:
References:
citation: 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.