NCT02404337

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
12

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Jul 2015

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 6, 2015

Completed
25 days until next milestone

First Posted

Study publicly available on registry

March 31, 2015

Completed
3 months until next milestone

Study Start

First participant enrolled

July 1, 2015

Completed
2.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2017

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2018

Completed
Last Updated

February 3, 2023

Status Verified

February 1, 2018

Enrollment Period

2.4 years

First QC Date

March 6, 2015

Last Update Submit

February 1, 2023

Conditions

Homocystinuria

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (2)

  • 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

Study Arms (2)

100 mg/kg of Betaine

EXPERIMENTAL

Dose 1 : 100 mg/kg of Betaine

Drug: Betaine

250 mg/kg of Betaine

EXPERIMENTAL

Dose 2 : 250 mg/kg of Betaine

Drug: Betaine

Interventions

BetaineDRUG
100 mg/kg of Betaine250 mg/kg of Betaine

Eligibility Criteria

Age1 Year - 18 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • ≥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

You may not qualify if:

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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Assistance Publique - Hôpitaux de Paris

Paris, 75019, France

Location

Related Publications (1)

  • 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: 36376887RESULT

MeSH Terms

Conditions

Homocystinuria

Interventions

Betaine

Condition Hierarchy (Ancestors)

Brain Diseases, Metabolic, InbornBrain Diseases, MetabolicBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesHyperhomocysteinemiaAmino Acid Metabolism, Inborn ErrorsMetabolism, Inborn ErrorsGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesConnective Tissue DiseasesSkin and Connective Tissue DiseasesMetabolic DiseasesNutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Trimethyl Ammonium CompoundsQuaternary Ammonium CompoundsAminesOrganic ChemicalsOnium Compounds

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 6, 2015

First Posted

March 31, 2015

Study Start

July 1, 2015

Primary Completion

December 1, 2017

Study Completion

February 1, 2018

Last Updated

February 3, 2023

Record last verified: 2018-02

Locations

FR(1)