Acetazolamide (AZ) for Management of Alkalosis in Bartter Syndrome (AZ)

Acetazolamide (AZ) for Management of Refractory Hypokalemia Metabolic Alkalosis in Bartter Syndrome

In this prospective controlled cross over clinical trial, the investigators aim to evaluate the efficacy and safety of acetazolamide for the management of metabolic alkalosis in children with Bartter syndrome. Urine and blood electrolytes will be measured before and after acetazolamide treatment. The primary end point is a change in polyuria, hypokalemia, and metabolic alkalosis.

Study Overview

• Status: Unknown
• Conditions: Bartter Syndrome
• Intervention / Treatment: Drug: Acetazolamide

Detailed Description

Bartter syndrome is a hereditary salt-loosing tubulopathy caused by several gene mutations encoding the sodium reabsorption in the thick ascending limb of loop of Henle, with poor response to treatment. The effects of inhibition of proximal tubular reabsorption of bicarbonate by acetazolamide have not been previously studied in Batter patients.

The present study is designed to assess he efficacy and safety of acetazolamide for the management of children with Bartter syndrome. The primary end point is change in polyuria, hypokalemia, and metabolic alkalosis.

In this prospective observational crossover clinical trial, patients between ages 1 and 10 years with clinical diagnosis of Bartter syndrome (hypokalemia, metabolic alkalosis, normal blood pressure, elevated urine chloride >20 milliequivalent per liter, high serum aldosterone and plasma renin levels) will be enrolled in a 4- week clinical trial. After initial clinical and laboratory evaluations, patients will receive acetazolamide 5.0 mg/kg orally as a single daily dose and each patient will act as his/her own control. Renal electrolyte and 24-hour urine output will be measured at baseline and after the 4 weeks acetazolamide treatment.

• Study Type: Observational
• Enrollment (Anticipated): 20

Contacts and Locations

• Study Contact: Name: Farahnak Assadi, MD; Phone Number: 3125600477; Email: fassadi@rush.edu
• Study Contact Backup: Name: Mojgan Mazaheri, MD; Phone Number: 00-98 9123069789; Email: mojganmazaheri@yahoo.com

Study Locations

• Iran, Islamic Republic of
  • Mashhad, Iran, Islamic Republic of
    • Recruiting
    • Fateme Ghane Sharbaf
    • Contact: Fateme Ghane Sharbaf, MD; Phone Number: 00 98 9153112139; Email: ghanesharbaf@gmail.com
    • Contact: Farahnak Assadi; Phone Number: 3125600477; Email: fassadi@rush.edu
  • Semnan, Iran, Islamic Republic of, 011000
    • Recruiting
    • Semnan University of Medical Sciences
    • Contact: Farahnak Assadi, MD; Phone Number: 3125600477; Email: fassadi@rush.edu
    • Contact: Mojgan Mazaheri, MD; Phone Number: 9123069789; Email: mojganmazaheri@yahoo.com
  • Tehran, Iran, Islamic Republic of
    • Not yet recruiting
    • Banafshe Dormansh
    • Contact: Banafshe Dormanesh, MD; Phone Number: 00 98 9123886725; Email: dr.dormansh@yahoo.com
    • Contact: Farahnak Assadi, MD; Phone Number: 3125600477; Email: Farahnak_Assadi@rush.edu
  • Zahedan, Iran, Islamic Republic of
    • Recruiting
    • Simin Sadeghi
    • Contact: Farahnak Assadi, MD; Phone Number: 3125600477; Email: fassadi@rush.edu
    • Contact: Simin Sadeghi, MD; Phone Number: 00 98 54533295573; Email: sisadegh@yahoo.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 10 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Children between 1 and 10 years of age with failure to thrive, polyuria and unexplained hypokalemic metabolic alkalosis will be recruited for this trial.

Description

Inclusion Criteria:

• Hypokalemia
• metabolic alkalosis
• normal blood pressure
• random urine chloride >20 milliequivalent per liter (mEq/L)
• Elevated serum aldosterone and renin levels

Exclusion Criteria:

• Hypertension
• History of emesis
• Prior use of laxatives
• Cystic fibrosis ofpancrease

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Crossover
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Acetazolamide; Oral administration of acetazolamide 5 mg/kg/day for 4 weeks	Drug: Acetazolamide; Correction of metabolic alkalosis by inhibition of the filtered bicarbonate load reabsorption in the proximal tubules using acetazolamide (AZ)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Metabolic alkalosis	Change in serum bicarbonate level	4 weeks
Urine output	Change in 24-hr urine volume	4 weeks

Collaborators and Investigators

• Sponsor: Tehran University of Medical Sciences
• Investigators: Study Director: Farahnak Assadi, MD, Rush University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): January 10, 2019
• Primary Completion (Anticipated): October 30, 2019
• Study Completion (Anticipated): December 30, 2019

Study Registration Dates

• First Submitted: February 16, 2019
• First Submitted That Met QC Criteria: February 19, 2019
• First Posted (Actual): February 20, 2019

Study Record Updates

• Last Update Posted (Actual): February 20, 2019
• Last Update Submitted That Met QC Criteria: February 19, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: Acetazolamide; Hypokalemic metabolic alkalosis; Bartter syndrome
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Kidney Diseases; Urologic Diseases; Endocrine System Diseases; Disease; Renal Tubular Transport, Inborn Errors; Adrenocortical Hyperfunction; Adrenal Gland Diseases; Acid-Base Imbalance; Hyperaldosteronism; Syndrome; Bartter Syndrome; Alkalosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Carbonic Anhydrase Inhibitors; Natriuretic Agents; Diuretics; Anticonvulsants; Acetazolamide
• Other Study ID Numbers: Acetazolamide (AZ)

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.: No