Ignite Creation Date:
2024-05-05 @ 4:38 PM
Last Modification Date:
2024-10-26 @ 9:22 AM
Study NCT ID:
NCT00283387
Status:
COMPLETED
Last Update Posted:
2013-12-16
First Post:
2006-01-26
Brief Title:
Efficacy of Betaine for Reduction of Urine Oxalate in Patients With Type 1 Primary Hyperoxaluria
Sponsor:
Mayo Clinic
Organization:
Mayo Clinic
Study Overview
Official Title:
Efficacy of Betaine for Reduction of Urine Oxalate in Patients With Type 1 Primary Hyperoxaluria
Status:
COMPLETED
Status Verified Date:
2013-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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
Hypothesis
Betaine will effectively reduce urine oxalate excretion in Primary Hyperoxaluria Type I patients
Detailed Description:
Our prior genotyping results have shown an association between the G170R allele and the clinical response to VB6 Patients homozygous for this change show a complete response and heterozygous patients a partial response Since VB6 is a safe and completely effective treatment for patients homozygous for G170R we will not study betaine in this group Instead 20 participants older than 6 years of age who are G170R compound heterozygous non-G170R missense or truncating sequence change homozygous or heterozygous will be selected for enrollment Participants in whom VB6 provides a partial reduction in urine oxalate excretion compound heterozygotes for the G170R mutation will be maintained on a stable dose of VB6 8 mgkgd for two months before and throughout betaine treatment Those who have demonstrated no response to VB6 will receive betaine alone
Participants will be randomized to receive either betaine or placebo for the first 2 month arm of the study Following 2 months of treatment and 2 months of washout each participant will cross over to the other arm of the study The other arm will consist of the participant being on 2 months of treatment of whatever they were not taking in the first arm betaine vs placebo Neither the study staff nor the participant will know whether the participant is taking betaine for the first or second arm of the study or the placebo for the first or second arm of the study Only the pharmacy will know this
Prior to the study a complete history and physical examination and baseline laboratory studies pertinent to the routine care of primary hyperoxaluria patients will be performed Complete Blood Count CBC with differential chemistry group electrolytes plasma oxalate and creatinine clearance urinary supersaturation All women capable of reproduction will receive a pregnancy test prior to enrollment
Participant will complete two 24-hour urine collections for calcium oxalate super-saturation includes 24-hour urine oxalate excretion at baseline inclusive of creatinine determination for assessment of completeness They will then begin Cystadane anhydrous solution 12 gramsday in subjects younger than 10 years of age and 20 gramsday in subjects 10 years of age and older in two divided doses These doses of betaine have been shown to effectively treat pediatric patients with VB6-resistant homocystinuria and reverse Nonalcoholic Steatohepatitis NASH in adult patients so we expect they will achieve sufficient intra-hepatocyte levels to have an effect in PHI
A sample of each 24-hour urine will be stored frozen -80ºC to allow determination of indicators of oxidant stress should urinary oxalate fall
If effective betaine could represent a new and safe treatment option for a subset of PHI patients particularly those with either partially VB6 responsive or VB6 refractory hyperoxaluria or those with adverse effects such as peripheral neuropathy from large doses of VB6 We do not anticipate any adverse medication effects specific to primary hyperoxaluria However as an extra safeguard for children with PHI ten subjects older than 15 years of age will be tested first and if the agent is well tolerated in PHI patients pediatric subjects older than 6 years of age will then be recruited for participation
Participants will be randomized to receive either betaine or placebo for the first 2 month arm of the study Following 2 months of treatment and 2 months of washout each participant will cross over to the other arm of the study The other arm will consist of the participant being on 2 months of treatment of whatever they were not taking in the first arm betaine vs placebo Neither the study staff nor the participant will know whether the participant is taking betaine for the first or second arm of the study or the placebo for the first or second arm of the study Only the pharmacy will know this
Prior to the study a complete history and physical examination and baseline laboratory studies pertinent to the routine care of primary hyperoxaluria patients will be performed Complete Blood Count CBC with differential chemistry group electrolytes plasma oxalate and creatinine clearance urinary supersaturation All women capable of reproduction will receive a pregnancy test prior to enrollment
Participant will complete two 24-hour urine collections for calcium oxalate super-saturation includes 24-hour urine oxalate excretion at baseline inclusive of creatinine determination for assessment of completeness They will then begin Cystadane anhydrous solution 12 gramsday in subjects younger than 10 years of age and 20 gramsday in subjects 10 years of age and older in two divided doses These doses of betaine have been shown to effectively treat pediatric patients with VB6-resistant homocystinuria and reverse Nonalcoholic Steatohepatitis NASH in adult patients so we expect they will achieve sufficient intra-hepatocyte levels to have an effect in PHI
A sample of each 24-hour urine will be stored frozen -80ºC to allow determination of indicators of oxidant stress should urinary oxalate fall
If effective betaine could represent a new and safe treatment option for a subset of PHI patients particularly those with either partially VB6 responsive or VB6 refractory hyperoxaluria or those with adverse effects such as peripheral neuropathy from large doses of VB6 We do not anticipate any adverse medication effects specific to primary hyperoxaluria However as an extra safeguard for children with PHI ten subjects older than 15 years of age will be tested first and if the agent is well tolerated in PHI patients pediatric subjects older than 6 years of age will then be recruited for participation
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 5R01DK073354-04 | NIH | None | httpsreporternihgovquickSearch5R01DK073354-04 |