Obesity and Uric Acid Stones Study

Phase 3

Completed

• Conditions: Obesity; Type 2 Diabetes Mellitus in Obese; Pre-Diabetes; Uric Acid Stones
• Interventions: Drug: Phentermine / Topiramate Oral Product; Combination Product: Citrate Salts, Allopurinol, Diet

• Registration Number: NCT04621929
• Lead Sponsor: University of Florida

Brief Summary

The investigator proposes an 18 month, feasibility pilot study, randomizing obese and diabetic individuals with pure uric acid nephrolithiasis (UAN) or mixed calcium oxalate (CO) UAN to either phentermine/topiramate or a pragmatic control group who will remain on their standard medication regimen (citrate salts, allopurinol, diet, etc.).

Detailed Description

Mounting evidence indicates that obesity, diabetes mellitus, and kidney stones are inter-connected diseases, particularly uric acid nephrolithiasis (UAN) with or without components of calcium oxalate (CO). Obese or overweight diabetics have a six-fold increased risk to develop UAN/COUAN due to the inability to properly add buffer (ammonium) to urine. Of the FDA approved drugs in the weight loss market, the combination medication phentermine/ topiramate is the most effective and has a unique side effect of alkalinizing the urine (making it less acidic). The hypothesize of this project is that treatment of obese, diabetic patients with phentermine/topiramate will reduce the incidence of UAN/COUAN by 1) direct urinary alkalinization and 2) weight loss. Weight loss will indirectly improve urinary buffering ability through improvement in insulin sensitivity and will decrease renal oxidative stress. The investigative team proposes an 18 month, feasibility pilot study, randomizing 30 obese and diabetic individuals with UAN/COUAN to either phentermine/topiramate (n=20) or a pragmatic control group (n=10) who would remain on standard medication regimen (citrate salts, allopurinol, diet, etc).

Study Timeline

• Study First Submitted: 2020-11-03
• Study First Submitted QC: 2020-11-06
• Study First Posted: 2020-11-09
• Study Start: 2021-03-31
• Status Verified: 2024-11
• Primary Completion: 2024-11-14
• Study Completion: 2024-11-14
• Last Update Submitted: 2025-03-25
• Last Update Posted: 2025-03-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 22

Inclusion Criteria

• have recurrent pure uric acid nephrolithiasis (UAN) or mixed calcium oxalate (CO)/UAN. Recurrent stone disease is defined as at least two spontaneous kidney stone passages, two previous kidney stone procedures, or one previous stone passage and one previous procedure. Pure UAN is defined as at least one previous stone analysis demonstrating 100% uric acid mineral content. Mixed COUAN will be defined as at least one previous stone analysis with any mix of uric acid ≥80% and ≤20% calcium oxalate. If participant has more than one stone analysis, the most recent will be considered the current stone type.
• have obesity, defined as BMI > 30 kg/m2.
• have type 2 diabetes mellitus or pre-diabetes, defined as previously diagnosed by laboratory testing (hemoglobin A1c, fasting plasma glucose, or oral glucose tolerance test) or as demonstrated by use of anti-hyperglycemic medications or insulin.
• have at least one 24-hour urine study off medications demonstrating urine pH < 5.8 or a study 24-hr urine demonstrating urine pH < 5.8

Exclusion Criteria

• contraindications to topiramate, including: recurrent major depression, current substantial depressive symptoms, uncontrolled depression by PHQ 9 score >= 10, history of suicidal ideation or behavior with intent to act (versus exclude those with depression); current pregnancy or attempting to conceive; pre-existing chronic kidney disease with eGFR < 60 at time of enrollment; active cancer or active treatment for cancer (chemotherapy, radiation); and non-ambulatory.
• contraindications to phentermine, including: unstable cardiovascular disease defined as decompensated heart failure, unstable angina, atrial fibrillation, uncontrolled blood pressure (>160 systolic), hyperthyroidism; monoamine oxidase inhibitor use; current history of drug or alcohol abuse.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Allocated to intervention/treatment	Phentermine / Topiramate Oral Product	Daily phentermine/topiramate x 18 months
Allocated to pragmatic control	Citrate Salts, Allopurinol, Diet	Remain on their current regimen

Primary Outcome Measures

Name	Time	Method
Kidney stone growth (mm2) as determined by non-contrast CT scan	18 months	Existing kidney stone growth
New kidney stone formation (mm2) as determined by non-contrast CT scan	18 months	Formation of a new kidney stone

Secondary Outcome Measures

Name	Time	Method
Change in hemoglobin A1c	18 months	Percent change in A1c (end of study compared to baseline)
Change in urinary calcium parameters	18 months	Percent change in urinary calcium
Change in urinary pH parameters	18 months	Absolute change in urine pH (end of study compared to baseline)
Change in urinary uric acid parameters	18 months	Percent change in urinary uric acid
Change in weight	18 months	Expressed as total percent body weight loss (total weight loss in pounds/starting weight in pounds)
Change in urinary citrate parameters	18 months	Percent change in urinary citrate

Trial Locations

Locations (1)

University of Florida; 🇺🇸 Gainesville, Florida, United States