Use of Oral Probiotics to Reduce Urinary Oxalate Excretion

Crohn's Disease Clinical Trial

Official title:

Use of Oral Probiotics to Reduce Urinary Oxalate Excretion

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00587041
• Other study ID #: 1483-05
• Secondary ID: R21AT002534UL1RR
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: December 21, 2007
• Last updated: April 28, 2012
• Start date: February 2006
• Est. completion date: July 2009

Study information

• Verified date: April 2012
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The purpose of this study was to determine the effect of two probiotic preparations (Agri-King Synbiotic and Oxadrop) on urinary oxalate excretion in patients with mild hyperoxaluria. Probiotics are live microorganisms thought to be beneficial to the host organism. Hyperoxaluria is a hereditary disorder that causes a special kind of stone to form in the kidney and urine. Oxalates are naturally-occurring substances found in plants, animals, and in humans. Excretion of oxalates in the urine is a risk factor for kidney stone formation.

Our hypothesis was that the mild hyperoxaluria is due to over absorption of oxalate from food and that probiotics will improve gastrointestinal barrier function to decrease oxalate absorption across the gut (and hence its elimination in the urine).

In the study, participants were randomized to placebo, Agri-King Synbiotic, or Oxadrop, and were treated for 6 weeks. Patients were maintained on a controlled diet to remove the confounding variable of differing oxalate intake and availability from food.

Description:

Renal manifestations of chronic hyperoxaluria include nephrolithiasis and, when extreme, interstitial scarring and progressive loss of function. The clinical outcome can be dismal. Although primary hyperoxaluria is relatively rare, hyperoxaluria secondary to gastrointestinal malabsorption is not. Furthermore, the formation of calcium oxalate kidney stones is extremely common, and evidence suggests that minimal, perhaps transient elevations in urinary oxalate concentration may be an important factor in at least a subgroup of these patients with "idiopathic" calcium oxalate urolithiasis. In the case of enteric hyperoxaluria the pathogenic role of oxalate is clear, and renal scarring is commonly observed as a consequence of oxalate exposure and calcium oxalate crystal deposition, in addition to stones. Unfortunately, few satisfactory specific treatments for enteric hyperoxaluria are available. Typical strategies include dietary restriction of oxalate to limit its delivery to the colon; low fat diets to limit malabsorption and distal colonic effects of fatty acids and bile acids; oral calcium to bind oxalate; and bile acid sequestrants like cholestyramine. In its entirety, this regimen is quite rigorous for patients, and even if compliance is achieved the therapy is not always effective. Previous studies have shown that components of the endogenous digestive microflora can utilize oxalate, potentially limiting its absorption from the intestinal lumen. A recent preliminary study demonstrated that a preparation of lactic acid bacteria degraded oxalate in vitro and reduced urinary oxalate excretion when given by mouth. We have recently demonstrated that the same preparation of lactic acid bacilli (Oxadrop) can reduce urinary oxalate excretion in patients with enteric hyperoxaluria. In the current proposal, in a placebo-controlled trial we will determine the effectiveness of this and another probiotic preparation (Agri-King Synbiotic) [AKSB] for the treatment of hyperoxaluria in patients with mild hyperoxaluria, as well as enteric hyperoxaluria.

Specific Aims are: 1) Determine the effect of two probiotic preparations (AKSB and Oxadrop on urinary oxalate excretion in a well-defined group of patients with enteric hyperoxaluria; and 2) Determine the effect of two probiotic preparations (AKSB and Oxadrop) on urinary oxalate excretion in a well-defined group of patients with idiopathic calcium oxalate urolithiasis and mild hyperoxaluria. If results are positive, treatment for calcium oxalate kidney stones could be revolutionized.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: July 2009
• Est. primary completion date: July 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Enteric hyperoxaluria (>0.5 mM/day; > 45 mg/day) due to fat malabsorption from inflammatory bowel disease (Crohn's Disease). (Patients in remission maintained on stable doses of Remicade/Imuran/Methotrexate every 8 weeks can be recruited as long as the trial can be conducted between 5 and 8 weeks after the last dose); OR

• Enteric hyperoxaluria (>0.5 mM/day; > 45 mg/day) from gastric bypass procedures (gastric bypass for obesity, or other surgical causes of gastric dumping and fat malabsorption (e.g., antrectomy, vagotomy and pyloroplasty for gastric ulcers) (Patients with inflammatory bowel disease must be in clinical remission); OR

• Calcium oxalate nephrolithiasis and mild hyperoxaluria of unknown etiology (>0.35 mM/day) (n=60)

• Presence of radioopaque stones on x-ray, or a history consistent with passage of a stone or stone surgery or extracorporeal shock wave lithotripsy (ESWL) in the last 5 years and if on stone medication, doses have remained stable for at least 3 months

• Stone composition confirmed either by stone analysis demonstrating composition equal to or more than 50% calcium oxalate, or by radiographic demonstration of a calcific renal stone in the presence of hyperoxaluria

Exclusion Criteria:

• On immunosuppressive medications (excluding small stable doses of prednisone of 10 mg or less)

• Human immunodeficiency virus (HIV) infection, known enteric bacterial infection, or history of splenectomy

• Have a current malignancy, other than superficial skin cancers that have been excised, unless they felt to be in complete remission (> 5 years)

• Previous colectomy

• Have completed a course of oral or parenteral antibiotics less than 2 weeks before initiation of the study (patients who require a course of antibiotics during the period of preparation administration will be withdrawn from the study and excluded from the final analysis)

• Patient pregnant or breast-feeding

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Crohn Disease
• Crohn's Disease
• Hyperoxaluria
• Nephrolithiasis

Intervention

Dietary Supplement:
• Oxadrop
Oxadrop 1 packet daily plus 1 placebo capsule twice daily. Each gram of Oxadrop® contains 2x1011 bacteria (L. acidophilus, L. brevis, S. thermophilus, and B. infantis).
• Agri-King Synbiotic (AKSB)
AKSB 1 capsule twice daily plus 1 placebo packet daily. AKSB contains Fructo-oligosaccharide; Enterococcus faecium (SF68); Saccharomyces cerevisiae subspecies Boulardi; and Saccharomyces cerevisiae

Other:
• Placebo
1 placebo packet daily and 1 placebo capsule twice daily

Locations

Country	Name	City	State
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (5)

Lead Sponsor	Collaborator
Mayo Clinic	National Center for Complementary and Integrative Health (NCCIH), National Center for Research Resources (NCRR), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

References & Publications (1)

Lieske JC, Tremaine WJ, De Simone C, O'Connor HM, Li X, Bergstralh EJ, Goldfarb DS. Diet, but not oral probiotics, effectively reduces urinary oxalate excretion and calcium oxalate supersaturation. Kidney Int. 2010 Dec;78(11):1178-85. doi: 10.1038/ki.2010 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in 24-hour Urinary Supersaturation for Calcium Oxalate	Urine is often supersaturated, which favors precipitation of crystalline phases such as calcium oxalate. However, crystals do not always form in supersaturated urine because supersaturation is balanced by crystallization inhibitors that are also present. Supersaturation is calculated by measuring the concentration of all the ions that can interact. Once these concentrations are known, a computer program can calculate the theoretical supersaturation with respect to the important crystalline phases, eg, calcium oxalate. Values for supersaturated ions are expressed in units of Gibbs free energy.	Time zero (on diet but no drug), 6 weeks (on drug and diet)	No
Secondary	24 Hour Urine Oxalate Excretion	The amount of oxalate excreted in the urine over a 24 hour period, a risk for calcium oxalate kidney stones	At end of study, approximately 6 weeks	No

External Links

•   Mayo Clinic Clinical Trials