Use of Oral Probiotics to Reduce Urinary Oxalate Excretion

NCT00587041 | Completed Phase 1 Results DMC

• 4 other identifiers: 1483-05R21AT002534UL1RR024150P50DK083007
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Nephrolithiasis; Hyperoxaluria; Crohn's Disease

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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)

Secondary Outcomes (1)

• 24 Hour Urine Oxalate Excretion

  At end of study, approximately 6 weeks

Study Arms (3)

Placebo

PLACEBO COMPARATOR

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

Other: Placebo

Oxadrop

ACTIVE COMPARATOR

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)

Dietary Supplement: Oxadrop

Agri-King Synbiotic

ACTIVE COMPARATOR

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

Dietary Supplement: Agri-King Synbiotic (AKSB)

Interventions

Oxadrop 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).

Oxadrop

Agri-King Synbiotic (AKSB) 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

Also known as: AKSB

Agri-King Synbiotic

Placebo OTHER

1 placebo packet daily and 1 placebo capsule twice daily

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Mayo Clinic: lead
• National Institutes of Health (NIH): collaborator
• National Center for Complementary and Integrative Health (NCCIH): collaborator
• National Center for Research Resources (NCRR): collaborator
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Related 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.2010.310. Epub 2010 Aug 25.

  PMID: 20736987 RESULT

MeSH Terms

Conditions

Nephrolithiasis; Hyperoxaluria; Crohn Disease; Kidney Calculi; Calculi

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urolithiasis; Male Urogenital Diseases; Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Urinary Calculi; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

Small sample size, low oxalate levels in diet

Results Point of Contact

• Title: Use of Symbiotics to Reduce Urinary Oxalate Excretion
• Organization: Mayo Clinic

lieske.john@mayo.edu

507-266-7960

Study Officials

• John C Lieske, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: December 21, 2007
• First Posted: January 7, 2008
• Study Start: February 1, 2006
• Primary Completion: July 1, 2009
• Study Completion: July 1, 2009
• Last Updated: May 31, 2012
• Results First Posted: May 31, 2012

Record last verified: 2012-04

Locations

US (1)