Safety and Efficacy of Chlorthalidone in Type 1 Diabetes

Safety and Efficacy of Chlorthalidone to Reduce Urinary Calcium Excretion in Adolescents/Yount Adult With Type 1 Diabetes

This open-label study will determine if chlorthalidone is safe and effective for the use of reducing urinary calcium excretion over 4 weeks in subjects with type 1 diabetes

Study Overview

• Status: Terminated
• Conditions: Type 1 Diabetes Mellitus; Hypercalciuria
• Intervention / Treatment: Drug: Chlorthalidone

Detailed Description

Type 1 diabetes (T1D) is associated with increased urinary calcium loss, which may contribute to the low bone mineral density and increased fracture risk observed in patients with this condition. Chlorthalidone is a thiazide-like diuretic that is commonly used to reduce urinary calcium excretion in other conditions such as idiopathic hypercalciuria. Its safety and efficacy has not been specifically tested in an adolescent type 1 diabetes population.

T1D subjects with hypercalciuria and who meet inclusion/exclusion criteria will be given chlorthalidone daily. Blood and urine tests, blood pressure, and glycemic control will be assessed at weekly study visits for 4 weeks.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • Rochester, New York, United States, 14642
      • University of Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of T1D
• Age 12-21 years
• Tanner Stage 2 or greater pubertal development
• Urine calcium excretion ≥ 4 mg/kg/day
• Able to swallow pills

Exclusion Criteria:

• BMI > 99th percentile for age (<18 years) or BMI >35 kg/m2 (≥ 18 years)

• Coexistent conditions that may affect calcium metabolism including:

  • celiac disease
  • Graves' Disease
  • Addison's disease
  • hypo- or hyperparathyroidism

• History of diabetes related complications including:

  • neuropathy
  • retinopathy
  • nephropathy
  • gastroparesis
• History of oral or inhaled corticosteroid use for ≥ 5 consecutive days within the past month
• History of any diuretic use within the past month

• Laboratory abnormalities on screening bloodwork including:

  • estimated glomerular filtration rate <90 mL/min per 1.73 m2 of body surface area
  • serum calcium >10.5 mg/dL
  • serum potassium <3.5 mmol/L
• Systolic or diastolic blood pressure <5th percentile for age and sex50 for age <18 years or systolic <90 mmHg or diastolic blood pressure <60 mmHG for age ≥18 years

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Chlorthalidone; Chlorthalidone 12.5-50 mg by mouth daily for 4 weeks	Drug: Chlorthalidone; Chlorthalidone 12.5-5 mg by mouth daily for 4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Urinary Calcium Excretion	Change in 24 hour urine calcium excretion	Assessed at baseline and at 4 weeks
Hypokalemia	Serum potassium decreased to <3.5 milliequivalent/L	Assessed weekly for up to 4 weeks or until hypokalemia develops
Hypercalcemia	Serum calcium increased to >10.5 mg/dL	Assessed weekly for up to 4 weeks or until hypercalcemia develops
Hyperglycemia	Change in serum fructosamine	Assessed at baseline and at 4 weeks

Collaborators and Investigators

• Sponsor: University of Rochester
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Study record dates

Study Major Dates

• Study Start (Actual): June 28, 2019
• Primary Completion (Actual): June 1, 2020
• Study Completion (Actual): June 1, 2020

Study Registration Dates

• First Submitted: October 20, 2017
• First Submitted That Met QC Criteria: October 24, 2017
• First Posted (Actual): October 30, 2017

Study Record Updates

• Last Update Posted (Actual): January 5, 2021
• Last Update Submitted That Met QC Criteria: December 8, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: type 1 diabetes; hypercalciuria
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Urological Manifestations; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypercalciuria; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Natriuretic Agents; Membrane Transport Modulators; Diuretics; Sodium Chloride Symporter Inhibitors; Chlorthalidone
• Other Study ID Numbers: 66282; 1K23DK114477-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Data will be available in aggregate. No plan to share individual data at present.

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