Use of Oral Probiotics to Reduce Urinary Oxalate Excretion

NCT ID: NCT00587041

Last Updated: 2012-05-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-02-28
• Study Completion Date: 2009-07-31

Brief 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.

Detailed 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.

Conditions

Nephrolithiasis; Hyperoxaluria; Crohn's Disease

Keywords

Synbiotic; Urine Oxalate; Probiotic; Kidney Stone; Gastric Bypass; Crohn's; Stone; Hyperoxaluria; Enteric Hyperoxaluria

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Placebo

Participants received placebo for 6 weeks: 1 placebo packet daily and 1 placebo capsule twice daily

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

1 placebo packet daily and 1 placebo capsule twice daily

Oxadrop

Participants received Oxadrop for 6 weeks: 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)

Group Type: ACTIVE_COMPARATOR

Oxadrop

Intervention Type: DIETARY_SUPPLEMENT

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

Participants received AKSB for 6 weeks: AKSB 1 capsule twice daily plus 1 placebo packet daily. AKSB contains Fructo-oligosaccharide; Enterococcus faecium (SF68); Saccharomyces cerevisiae subspecies Boulardi; and Saccharomyces cerevisiae

Group Type: ACTIVE_COMPARATOR

Agri-King Synbiotic (AKSB)

Intervention Type: DIETARY_SUPPLEMENT

AKSB 1 capsule twice daily plus 1 placebo packet daily. AKSB contains Fructo-oligosaccharide; Enterococcus faecium (SF68); Saccharomyces cerevisiae subspecies Boulardi; and Saccharomyces cerevisiae

Interventions

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).

Intervention Type: DIETARY_SUPPLEMENT

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

Intervention Type: DIETARY_SUPPLEMENT

Placebo

1 placebo packet daily and 1 placebo capsule twice daily

Intervention Type: OTHER

Other Intervention Names

AKSB

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

National Center for Complementary and Integrative Health (NCCIH)

NIH

Sponsor Role: collaborator

National Center for Research Resources (NCRR)

NIH

Sponsor Role: collaborator

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role: collaborator

Mayo Clinic

OTHER

Sponsor Role: lead

Responsible Party

John Lieske

Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

John C Lieske, MD

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

Mayo Clinic

Rochester, Minnesota, United States

Countries

United States

References

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.2010.310. Epub 2010 Aug 25.

Reference Type: RESULT

PMID: 20736987 (View on PubMed)

Other Identifiers

R21AT002534

Identifier Type: NIH

Identifier Source: secondary_id

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UL1RR024150

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P50DK083007

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1483-05

Identifier Type: -

Identifier Source: org_study_id