Phentermine/Topiramate for Uric Acid Stones

NCT ID: NCT04621929

Last Updated: 2026-01-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-31
• Study Completion Date: 2024-11-14

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).

Conditions

Obesity; Uric Acid Stones; Type 2 Diabetes Mellitus in Obese; Pre-Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Allocated to intervention/treatment

Daily phentermine/topiramate x 18 months

Group Type: EXPERIMENTAL

Phentermine / Topiramate Oral Product

Intervention Type: DRUG

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)

Allocated to pragmatic control

Remain on their current regimen

Group Type: ACTIVE_COMPARATOR

Citrate Salts, Allopurinol, Diet

Intervention Type: COMBINATION_PRODUCT

Control participants will complete initial visit requirements and study enrollment and will be maintained on their current therapy.

Interventions

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)

Intervention Type: DRUG

Citrate Salts, Allopurinol, Diet

Control participants will complete initial visit requirements and study enrollment and will be maintained on their current therapy.

Intervention Type: COMBINATION_PRODUCT

Other Intervention Names

Duromine; Adipex-P; Lomaira; Suprenza; Trokendi XR; Topamax; Qudexy XR; Eprontia; Qsymia

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role: collaborator

University of Florida

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Benjamin Canales, MD

Role: PRINCIPAL_INVESTIGATOR

University of Florida

Locations

University of Florida

Gainesville, Florida, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

1R21DK122317-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB202001895-A-N

Identifier Type: -

Identifier Source: org_study_id