Clinical Trials

Use of Oral Probiotics to Reduce Urinary Oxalate Excretion

Location:

Trial status:

Closed

Why is this study being done?

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.

Who is eligible to participate?

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

What is involved?

Patients with calcium oxalate kidney stones and too much oxalate in the urine seen in the Nephrology and Gastroenterology clinics at the Mayo Clinic will be asked to participate.

You will be given a diet (3 meals per day) prepared in the Mayo Clinical Research Center for 6 days, 3 meals per day. This diet will have carefully controlled amounts of protein, calcium, and oxalate. You will collect two 24-hour urine samples to measure the baseline amount of oxalate in the urine on the final 2 days. You may also have a blood sample taken to measure C-reactive protein (a marker of disease activity) or pregnancy test if applicable.

You will be randomly put in one of three groups by chance (like the flip of a coin)

• Lactobacilli preparation (Oxadrop) and placebo


• AKSB and placebo


• Placebo paste and Pill

You will begin taking either a combination of Oxadrop/placebo, AKSB/placebo, or placebo pill/paste, twice daily for 5 weeks total. During the first four weeks patients will be asked to eat three meals daily and maintain a diet diary. You will also be asked to maintain a relatively constant diet, and avoid foods with high oxalate content or that contain live cultures (e.g., yogurt).

During the 5th week patients again will be given a diet (3 meals per day) prepared in the Mayo Clinical Research Center for 6 days, 3 meals per day. This diet will match that of the first week. Patients will collect two 24-hour urine samples to measure the amount of oxalate in the urine on the final 2 days, to compare with the initial values. Patients with Inflammatory Bowel Disease will also have a second blood sample taken to measure C-reactive protein (a marker of disease activity).

Stool cultures will also be obtained at baseline and week 6 for fecal lactobacilli, enterococci, and yeast to determine if there are changes in intestinal bacteria due to the probiotics.

At the end of the study you will be asked to complete a questionnaire to look for any side effects of the preparations.

How long is the study?

You will be in the study for 6 weeks.

Last updated: 04/28/2012

NCT ID:

NCT00587041