Efficacy of Betaine for Reduction of Urine Oxalate in Patients With Type 1 Primary Hyperoxaluria
Condition: Hyperoxaluria
MeSH terms: Hyperoxaluria, Primary
Intervention: Betaine; Placebo
Intervention description: Subjects were randomly assigned oral betaine 12 grams/day in subjects younger than 10 years of age, and 20 grams/day in subjects 10 years of age and older, in two divided doses, for 2 months.; Subjects received oral lactose placebo, in two doses daily, for 2 months.
Intervention MeSH terms: Betaine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 15.0
Sex: All
Minimum age: 6 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Primary Hyperoxaluria

Summary:

      The aim of this study is to assess the efficacy and safety of betaine in reducing urine
      oxalate excretion of Type 1 Primary Hyperoxaluria (PHI) patients.

      Hypothesis:

      Betaine will effectively reduce urine oxalate excretion in Primary Hyperoxaluria Type I
      patients.
    

Eligibility criteria:

        Inclusion Criteria:

          1. A definitive diagnosis of Type 1 Primary Hyperoxaluria (PHI) as confirmed by hepatic
             angiotensinogen (AGT) deficiency, biochemical criteria (marked hyperoxaluria and
             hyperglycolic aciduria) or mutation analysis (having a known PHI mutation)

          2. Alanine-glyoxylate aminotransferase (AGXT) genotype known

          3. Hyperoxaluria not fully corrected by 3 months of continuous Vitamin B6 (VB6) at doses
             of 8 mg/kg/d or more

          4. Males or females, 6-70 years of age, inclusive

          5. Preserved renal function, as defined by measured glomerular filtration rate (GFR) > 30
             ml/min/1.73 m^2

          6. Sexually active female patients of childbearing potential must practice adequate
             contraception during the treatment period and for 6 months after discontinuation of
             therapy. A pregnancy test obtained at entry prior to the initiation of treatment must
             be negative. Female patients must not be breast-feeding. Sexually active male patients
             must practice acceptable methods of contraception during the treatment period and for
             6 months after discontinuation of therapy.

          7. Written informed consent for participation in this study.

        Exclusion Criteria:

          1. Patients who are fully VB6 responsive (i.e., G170R homozygotes).

          2. Prior recipients of liver transplantation performed for correction of AGT deficiency.

          3. Pregnancy or breastfeeding

          4. Unwillingness of patient and/or partner to use contraception during treatment.

          5. Malignant disease (other than non-melanoma skin cancer) in the previous two years.

          6. Markedly reduced renal function (Stage IV Chronic Kidney Disease or measured or
             estimated GFR < 30 ml/min/1.73 m^2)

          7. Allergy to betaine or related compounds

          8. History of papilledema or increased intracranial pressure.