Obesity and Uric Acid Stones Study

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: Recruiting
• 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 (Estimated): 40
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: John Marks; Phone Number: 352-273-5618; Email: marksjg@ufl.edu

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32610
      • Recruiting
      • University of Florida
      • Contact: John Marks; Phone Number: 352-273-5618; Email: marksjg@ufl.edu
      • Principal Investigator: Benjamin Canales

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in weight	Expressed as total percent body weight loss (total weight loss in pounds/starting weight in pounds)	18 months
Change in urinary pH parameters	Absolute change in urine pH (end of study compared to baseline)	18 months
Change in hemoglobin A1c	Percent change in A1c (end of study compared to baseline)	18 months
Change in urinary citrate parameters	Percent change in urinary citrate	18 months
Change in urinary calcium parameters	Percent change in urinary calcium	18 months
Change in urinary uric acid parameters	Percent change in urinary uric acid	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 (Estimated): December 31, 2023
• Study Completion (Estimated): March 31, 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 (Estimated): June 13, 2023
• Last Update Submitted That Met QC Criteria: June 9, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Kidney Diseases; Urologic Diseases; Endocrine System Diseases; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Urolithiasis; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Obesity; Prediabetic State; Nephrolithiasis; Hypoglycemic Agents; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites; Protective Agents; Anticonvulsants; Appetite Depressants; Anti-Obesity Agents; Antioxidants; Free Radical Scavengers; Central Nervous System Stimulants; Gout Suppressants; Sympathomimetics; Allopurinol; Topiramate; Phentermine
• 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