Betaine METABOLISM OF PATIENTS With Homocystinuria

Study Overview
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Brief Summary
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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
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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.

Official Title
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Betaine METABOLISM OF PATIENTS With Homocystinuria

Conditions
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Homocystinuria

Intervention / Treatment
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* Drug: Betaine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 100 mg/kg of Betaine<br>Dose 1 : 100 mg/kg of Betaine | Drug: Betaine<br> <br> |
| Experimental: 250 mg/kg of Betaine<br>Dose 2 : 250 mg/kg of Betaine | Drug: Betaine<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | 10 weeks - at the end of follow-up of each patient | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |