A Phase 2 interventional study of Betaine and Placebo in Hyperoxaluria, sponsored by Mayo Clinic. Completed at 1 site in United States. Open to participants aged 6 Years to 70 Years. Per ClinicalTrials.gov, last updated 2013-12-16.
Sponsored by Mayo Clinic · Phase 2, Interventional, and Treatment
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.
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 mg/kg/d) 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 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). 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.
42 studies on the registry are indexed under Hyperoxaluria, Primary; 11 are open to participants now.
This study's enrollment of 15 is below the median of 24 across 26 interventional studies indexed under Hyperoxaluria, Primary.
Browse Hyperoxaluria, Primary studies →Mayo Clinic is the lead sponsor of 3,269 studies on the registry; 672 are open to participants now.
Of its 452 completed or terminated interventional studies of FDA-regulated products, 321 (71%) have results posted.
Compared within Hyperoxaluria, Primary, this study's primary condition as ClinicalTrials.gg classifies it; the registry's first condition term is Hyperoxaluria. The counts are of registry records indexed under each term, refreshed daily. How we classify →
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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. This was followed by a 2 month washout period. Subjects then received the alternative study medication, oral lactose placebo, in two doses daily, for 2 months.
Drug: Betaine · Drug: Placebo
Subjects were randomly assigned to receive oral lactose placebo, in two doses daily, for 2 months. This was followed by a 2 month washout period. Subjects then received the alternative study medication, 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.
Drug: Betaine · Drug: Placebo
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.
Also known as: Cystadane
Subjects received oral lactose placebo, in two doses daily, for 2 months.
Also known as: Lactose
Urinary Oxalate Excretion
The patients were randomly assigned oral betaine or placebo for 2 months, followed by a 2 month washout. Each patient then received the alternate study medication for 2 months. Urinary Oxalate Excretion was measured by oxalate oxidase. Two 24 hour urine collections were obtained at baseline, and during the eighth week of each study period.
Time frame: baseline, 2 months, 6 months
Subjects were recruited from Mayo Clinic, Rochester between October 2006 and September 2008.
| Milestone | Betaine First, Then Placebo | Placebo First, Then Betaine |
|---|---|---|
| Started | 6 | 7 |
| Completed | 5 | 5 |
| Not completed | 1 | 2 |
| Withdrew: Subject non-compliant | 1 | 1 |
| Withdrew: Withdrawal by subject | 0 | 1 |
| Milestone | Betaine First, Then Placebo | Placebo First, Then Betaine |
|---|---|---|
| Started | 5 | 5 |
| Completed | 5 | 5 |
| Not completed | 0 | 0 |
| Milestone | Betaine First, Then Placebo | Placebo First, Then Betaine |
|---|---|---|
| Started | 5 | 5 |
| Completed | 5 | 5 |
| Not completed | 0 | 0 |
The patients were randomly assigned oral betaine or placebo for 2 months, followed by a 2 month washout. Each patient then received the alternate study medication for 2 months. Urinary Oxalate Excretion was measured by oxalate oxidase. Two 24 hour urine collections were obtained at baseline, and during the eighth week of each study period.
| umol/mg | Betaine | Placebo |
|---|---|---|
| Urinary Oxalate Excretion | 1.43 ± 0.97 | 1.04 ± 0.71 |
Collected over Subjects will be followed for adverse events for the 6 months while on study.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Betaine | — | 0/13 (0%) | 11/13 (84.6%) |
| Placebo | — | 0/13 (0%) | 8/13 (61.5%) |
| Event | Betaine | Placebo |
|---|---|---|
| DyspepsiaGastrointestinal disorders | 10/13 | 7/13 |
| Diarrhea/loose stoolsGastrointestinal disorders | 6/13 | 6/13 |
| HeadacheGeneral disorders | 4/13 | 1/13 |
| ConstipationGastrointestinal disorders | 2/13 | 1/13 |
| Age, Continuous(years) | Entire Study Population |
|---|---|
| Mean | 20.1 (6 to 43) |
| Sex: Female, Male(Participants) | Entire Study Population |
|---|---|
| Female | 7 |
| Male | 6 |
| Region of Enrollment(participants) | Entire Study Population |
|---|---|
| United States | 13 |
| Glomerular Filtration Rate (GFR)(ml/min/1.73 m^2) | Entire Study Population |
|---|---|
| Mean | 79 (39 to 134) |
| Number of Subjects on Concomitant Medications(participants) | Entire Study Population |
|---|---|
| Vitamin B6 | 9 |
| Neutral Phosphate | 7 |
| Citrate | 3 |
This study is completed, as verified in Nov 2013. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Studies of the drug tested here: Betaine