Clinical trial NCT04621929: Obesity and Uric Acid Stones Study
Official title: Phentermine/tOpiramate to eND Obesity and Uric Acid Stones Trial (POuND OUT)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Obesity
Uric Acid Stones
Type 2 Diabetes Mellitus in Obese
Pre-Diabetes
Lead sponsor: University of Florida
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2020-11-09
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 2:1 ratio block site of 6
Primary purpose: TREATMENT

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).

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.

Primary outcomes:
measure: Kidney stone growth (mm2) as determined by non-contrast CT scan
timeFrame: 18 months
measure: New kidney stone formation (mm2) as determined by non-contrast CT scan
timeFrame: 18 months
Secondary outcomes:
measure: Change in weight
timeFrame: 18 months
measure: Change in urinary pH parameters
timeFrame: 18 months
measure: Change in hemoglobin A1c
timeFrame: 18 months
measure: Change in urinary citrate parameters
timeFrame: 18 months
measure: Change in urinary calcium parameters
timeFrame: 18 months
measure: Change in urinary uric acid parameters
timeFrame: 18 months
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: University of Florida
state: Florida
Study officials:
affiliation: University of Florida
name: Benjamin Canales, MD
role: PRINCIPAL_INVESTIGATOR
References: