Phentermine/Topiramate for Uric Acid Stones

Phentermine/tOpiramate to eND Obesity and Uric Acid Stones Trial (POuND OUT)

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.).

Study Overview

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

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 Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Allocated to intervention/treatment; Daily phentermine/topiramate x 18 months	Drug: Phentermine / Topiramate Oral Product; All participants in the experimental group will receive oral generic tablet phentermine (18.75 or 37.5 mg dose) and topiramate (daily 100 mg or 150 mg dose); Other Names: Topamax; Lomaira; Qsymia; Adipex-P; Trokendi XR; Qudexy XR; Duromine; Suprenza; Eprontia
Active Comparator: Allocated to pragmatic control; Remain on their current regimen	Combination product: Citrate Salts, Allopurinol, Diet; Control participants will complete initial visit requirements and study enrollment and will be maintained on their current therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Kidney Stone Size (mm^3) Determined by Non-contrast CAT Scan	Stone perimeter within each cut of CT image was outlined using semiautomated volume tool (region of interest pen tool, CT software "Visage Imaging") and tallied to calculate stone volume (mm^3) for each individual stone and recorded from right and left kidney from all study participants at baseline CT and at end of study CT (18 months)	Baseline, 18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weight (kg)	total weight (baseline and end of study)	Baseline, 18 months
Urinary pH Parameters	urine pH (baseline and end of study). The pH scale ranges from 0 to 14. A pH of 7 is neutral. A pH less than 7 is acidic. A pH greater than 7 is basic.	Baseline, 18 months
%Hemoglobin A1c	%A1c (baseline and end of study)	Baseline, 18 months
Urinary Citrate Parameters	urinary citrate (baseline and end of study)	Baseline, 18 months
Urinary Calcium Parameters	urinary calcium (baseline and end of study)	Baseline, 18 months
Urinary Uric Acid Supersaturation (SS)	Urinary uric acid SS (before and end of study). Urinary Uric Acid Supersaturation (SS) is not measured in a specific unit, as it is a ratio. Result below 1: The urine is undersaturated, meaning that crystals are more likely to dissolve than form. Result equal to 1: The urine is in equilibrium with uric acid, so crystals will not grow or shrink. Result above 1: The urine is supersaturated, and the risk for crystals to form and grow is increased. A higher value indicates a greater risk.	Baseline, 18 months

Collaborators and Investigators

• Sponsor: University of Florida
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Benjamin Canales, MD, University of Florida

Study record dates

Study Major Dates

• Study Start (Actual): March 31, 2021
• Primary Completion (Actual): November 14, 2024
• Study Completion (Actual): November 14, 2024

Study Registration Dates

• First Submitted: November 3, 2020
• First Submitted That Met QC Criteria: November 6, 2020
• First Posted (Actual): November 9, 2020

Study Record Updates

• Last Update Posted (Actual): June 15, 2026
• Last Update Submitted That Met QC Criteria: May 21, 2026
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nutrition Disorders; Metabolic Diseases; Overnutrition; Body Weight; Glucose Metabolism Disorders; Overweight; Hyperglycemia; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity; Glucose Intolerance; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Diet, Food, and Nutrition; Physiological Phenomena; Carbohydrates; Amines; Nutritional Physiological Phenomena; Purines; Phenethylamines; Ethylamines; Sugars; Amphetamines; Hexoses; Monosaccharides; Fructose; Ketoses; Topiramate; Allopurinol; Phentermine; Diet; Qsymia
• Other Study ID Numbers: IRB202001895-A-N; 1R21DK122317-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes