Use of Oral Probiotics to Reduce Urinary Oxalate Excretion

Use of Oral Probiotics to Reduce Urinary Oxalate Excretion

Sponsors

Lead sponsor: Mayo Clinic

Collaborator: National Institutes of Health (NIH)
National Center for Complementary and Integrative Health (NCCIH)
National Center for Research Resources (NCRR)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Source Mayo Clinic
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.

Overall Status Completed
Start Date February 2006
Completion Date July 2009
Primary Completion Date July 2009
Phase Phase 1/Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Change in 24-hour Urinary Supersaturation for Calcium Oxalate Time zero (on diet but no drug), 6 weeks (on drug and diet)
Secondary Outcome
Measure Time Frame
24 Hour Urine Oxalate Excretion At end of study, approximately 6 weeks
Enrollment 40
Condition
Intervention

Intervention type: Dietary Supplement

Intervention name: Oxadrop

Description: 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).

Arm group label: Oxadrop

Intervention type: Dietary Supplement

Intervention name: Agri-King Synbiotic (AKSB)

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

Arm group label: Agri-King Synbiotic

Other name: AKSB

Intervention type: Other

Intervention name: Placebo

Description: 1 placebo packet daily and 1 placebo capsule twice daily

Arm group label: Placebo

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

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Overall Official
Last Name Role Affiliation
John C Lieske, MD Principal Investigator Mayo Clinic
Location
facility Mayo Clinic
Location Countries

United States

Verification Date

April 2012

Responsible Party

Responsible party type: Principal Investigator

Investigator affiliation: Mayo Clinic

Investigator full name: John Lieske

Investigator title: Professor of Medicine

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 3
Arm Group

Arm group label: Placebo

Arm group type: Placebo Comparator

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

Arm group label: Oxadrop

Arm group type: Active Comparator

Description: 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)

Arm group label: Agri-King Synbiotic

Arm group type: Active Comparator

Description: 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

Study Design Info

Allocation: Randomized

Intervention model: Parallel Assignment

Primary purpose: Treatment

Masking: Triple (Participant, Care Provider, Investigator)

Source: ClinicalTrials.gov