Hyperoxaluria
Conditions
Keywords
Hyperoxaluria, Oxazyme, oxalate, enteric hyperoxaluria
Brief summary
Hypothesis: Oral administration of the oxalate metabolizing enzyme Oxazyme (OC4) will degrade food-borne oxalate and hence prevent its absorption from the gastrointestinal tract. In addition, by reducing oxalate concentrations in the gastrointestinal fluid, oxalate secretion from blood to the intestinal tract may be increased. Both effects would decrease blood levels of oxalate, and hence oxalate excretion in the urine.
Detailed description
Oxazyme is an oxalate degrading compound that can potentially degrade food-borne oxalate and hence prevent its absorption from the gastrointestinal tract. We propose a 20-patient open-label trial pilot study of one month of Oxazyme twice daily (1gm Oxazyme sachet dissolved in 150 ml water) among adult subjects with a history of calcium oxalate nephrolithiasis. Patients will be stratified into those with enteric hyperoxaluria after Roux-en-Y Gastric Bypass (RYGB, n=10) and those with idiopathic hyperoxaluria (n=10). The patients will perform two, 24-hour, urine collections immediately before starting Oxazyme and on the last two days of the treatment period.
Interventions
DRUGOxazyme
Oxazyme (registered trademark) is a non-systemic orally delivered drug composed of recombinant oxalate decarboxylase (OxDC). It is formulated to enzymatically degrade available dietary oxalate prior to its absorption. Dosing: 1gm Oxazyme containing approximately 1600 Units OxDC in a sachet administered BID together with lunch and dinner. Subjects were instructed to open the oxazyme sachets and either sprinkle on food or add to a glass of water or fruit juice and consume the contents with a meal twice daily.
Sponsors
OxThera
Mayo Clinic
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Roux-en-Y gastric bypass hyperoxaluric Calcium oxalate (CaOx) stone subjects or Idiopathic hyperoxaluric CaOx stone subjects * Patients must have or had radio-opaque stones present on x-ray, or a history consistent with the passage of a stone or stone surgery or Extracorporeal Shock Wave Lithotripsy (ESWL) in the last 5 years. * Hyperoxaluria Ox/Cr ratio ≥36 mg/g * The patient must be able to provide written informed consent * Patients must be able to urinate reliably into a collection vessel to measure urine volume. * Patients may be taking drugs for the prevention of stone disease, including pyridoxine, thiazides, citrate supplements and allopurinol, as long as there have been no changes in these medications for at least 3 months
Exclusion criteria
* Primary hyperoxaluria patients * Use of Oxadrop, Oxabsorb, or other therapies affecting oxalate absorption from the gut, other than stable doses of calcium. * Subjects who are pregnant. Women of childbearing potential must have a negative pregnancy test prior to enrollment and must practice some form of birth control during the trial. * Patients on an unstable dose of any other drugs for the prevention of stone disease (i.e., pyridoxine, citrate supplements. etc.). Patients should have been on a stable dose for at least 3 months prior to randomization.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Urinary Oxalate Creatinine Ratio | Baseline, Week 4 | The urinary oxalate per creatinine ratio is expressed as mg/g. Paired t-test will be used when comparing reduction of urinary oxalate resulting from treatment (versus baseline) for each subject group. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total Urinary Oxalate Excretion | Baseline, 4 weeks | Oxalate is a salt of oxalic acid produced by the body's metabolism and excreted in the urine, measured in this study in two, 24-hour, urine collections. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from the Mayo Clinic, Rochester, Minnesota.
Pre-assignment details
7 subjects were enrolled on the Idiopathic arm; of these 2 did not complete baseline collections, and 3 didn't qualify, so these 5 were excluded. 15 subjects were enrolled on the RYGB arm; of these, 3 never started the study and 2 did not qualify, so these 5 were excluded.
Participants by arm
| Arm | Count |
|---|---|
| RYGB CaOx Stone Formers Subjects with enteric hyperoxaluria after Roux-en-Y Gastric Bypass (RYGB).
Dosing: 1gm Oxazyme containing approximately 1600 Units OxDC in a sachet administered BID together with lunch and dinner. Subjects were instructed to open the oxazyme sachets and either sprinkle on food or add to a glass of water or fruit juice and consume the contents with a meal twice daily. | 8 |
| Idiopathic Hyperoxaluria CaOx Stone Formers Subjects with idiopathic hyperoxaluria.
Dosing: 1gm Oxazyme containing approximately 1600 Units OxDC in a sachet administered BID together with lunch and dinner. Subjects were instructed to open the oxazyme sachets and either sprinkle on food or add to a glass of water or fruit juice and consume the contents with a meal twice daily. | 2 |
| Total | 10 |
Baseline characteristics
| Characteristic | RYGB CaOx Stone Formers | Idiopathic Hyperoxaluria CaOx Stone Formers | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 0 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 2 Participants | 8 Participants |
| Region of Enrollment United States | 8 participants | 2 participants | 10 participants |
| Sex: Female, Male Female | 5 Participants | 0 Participants | 5 Participants |
| Sex: Female, Male Male | 3 Participants | 2 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 8 | 0 / 2 |
| serious Total, serious adverse events | 0 / 8 | 0 / 2 |
Outcome results
Primary
Urinary Oxalate Creatinine Ratio
The urinary oxalate per creatinine ratio is expressed as mg/g. Paired t-test will be used when comparing reduction of urinary oxalate resulting from treatment (versus baseline) for each subject group.
Time frame: Baseline, Week 4
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RYGB CaOx Stone Formers | Urinary Oxalate Creatinine Ratio | Baseline | 68.6 mg/g | Standard Deviation 36.4 |
| RYGB CaOx Stone Formers | Urinary Oxalate Creatinine Ratio | Week 4 | 49.6 mg/g | Standard Deviation 27.9 |
| Idiopathic Hyperoxaluria CaOx Stone Formers | Urinary Oxalate Creatinine Ratio | Baseline | 38.7 mg/g | Standard Deviation 6.9 |
| Idiopathic Hyperoxaluria CaOx Stone Formers | Urinary Oxalate Creatinine Ratio | Week 4 | 34.7 mg/g | Standard Deviation 6.8 |
Comparison: Comparison of Urinary oxalate before and at the end of 4 weeks on Oxazyme in the RYGB Calcium oxalate (CaOx) Stone Formers arm.p-value: 0.027t-test, 2 sided
Comparison: Comparison of Urinary oxalate before and at the end of 4 weeks on Oxazyme in the Idiopathic Hyperoxaluria CaOx Stone Formers arm.p-value: 0.14t-test, 2 sided
Secondary
Total Urinary Oxalate Excretion
Oxalate is a salt of oxalic acid produced by the body's metabolism and excreted in the urine, measured in this study in two, 24-hour, urine collections.
Time frame: Baseline, 4 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RYGB CaOx Stone Formers | Total Urinary Oxalate Excretion | Baseline | 66.3 mg/24 hrs | Standard Deviation 28 |
| RYGB CaOx Stone Formers | Total Urinary Oxalate Excretion | 4 Weeks | 44.5 mg/24 hrs | Standard Deviation 23.7 |
| Idiopathic Hyperoxaluria CaOx Stone Formers | Total Urinary Oxalate Excretion | Baseline | 43.2 mg/24 hrs | Standard Deviation 5.9 |
| Idiopathic Hyperoxaluria CaOx Stone Formers | Total Urinary Oxalate Excretion | 4 Weeks | 32.3 mg/24 hrs | Standard Deviation 3.2 |
Comparison: Comparison of Oxalate before and at the end of 4 weeks on Oxazyme in the RYGB CaOx Stone Formers arm.p-value: 0.018t-test, 2 sided
Comparison: Comparison of Oxalate before and at the end of 4 weeks on Oxazyme in the Idiopathic Hyperoxaluria CaOx Stone Formers arm.p-value: 0.06t-test, 2 sided