Salt Supplementation in Gitelman Syndrome

Exploratory Study Into the Effect of Salt Supplementation in Gitelman Syndrome

The purpose of this study is to determine the effect of salt (NaCl) supplementation on serum potassium and clinical signs and symptoms in patients with Gitelman syndrome.

Study Overview

• Status: Completed
• Conditions: Gitelman Syndrome
• Intervention / Treatment: Other: Placebo; Dietary supplement: Salt (NaCl)

Detailed Description

Single subject multiple randomized double-blinded multi-crossover placebo-controlled trials (N-of-1 trials) will be performed. Participants will enroll the study after giving written informed consent. The individual trials will consist of 3 treatment blocks which each contain a 4-week treatment period of salt supplementation (12 grams of NaCl) and a 4-week treatment period of placebo, in a randomized, blinded order. After each period of 4 weeks, outcomes measures will be measured.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Naples, Italy
    • University Hospital of University of Campania "L. Vanvitelli"
• Netherlands
  • Gelderland
    • Nijmegen, Gelderland, Netherlands, 6500HB
      • Radboudumc
  • Zuid-Holland
    • Rotterdam, Zuid-Holland, Netherlands, 3000CA
      • Erasmus MC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Genetically-proven, symptomatic Gitelman syndrome
• Written informed consent

Exclusion Criteria:

• inability to discontinue potassium-sparing diuretics, mineralocorticoid antagonists and NSAIDs; this means inability to reach a potassium level of 2.5 mmol/L or higher with maximally tolerable potassium supplementation after discontinuation of potassium-sparing diuretics
• pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Salt (NaCl); 12 grams (12 capsules) of NaCl per day Note: participants will be treated with active and placebo comparator (N-of-1 trial design)	Dietary supplement: Salt (NaCl); 12 grams of salt (NaCl) per day
Placebo Comparator: Placebo; 12 capsules of placebo per day Note: participants will be treated with active and placebo comparator (N-of-1 trial design)	Other: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in serum Potassium	Change in serum potassium	Baseline, week 4, week 8, week 12, week 16, week 20, week 24
Change in symptoms measured by personalized symptom score sheet	Symptoms will be scored via a personalized symptom score sheet, which will be composed with the individual participant. Symptoms will be scored at a range from 0 - 10	Weekly (week 0 till week 24)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in serum sodium	Change in serum sodium	Baseline, week 4, week 8, week 12, week 16, week 20, week 24
Change in serum magnesium	Change in serum magnesium	Baseline, week 4, week 8, week 12, week 16, week 20, week 24
Change in serum chloride	Change in serum chloride	Baseline, week 4, week 8, week 12, week 16, week 20, week 24
Change in serum bicarbonate	Change in serum bicarbonate	Baseline, week 4, week 8, week 12, week 16, week 20, week 24
Change in serum calcium	Change in serum calcium	Baseline, week 4, week 8, week 12, week 16, week 20, week 24
Change in serum creatinine	Change in serum creatinine	Baseline, week 4, week 8, week 12, week 16, week 20, week 24
Change in serum aldosterone	Change in serum aldosterone	Baseline, week 4, week 8, week 12, week 16, week 20, week 24
Change in serum renin	Change in serum renin	Baseline, week 4, week 8, week 12, week 16, week 20, week 24
Change in fractional urinary excretion of potassium	Change in fractional urinary excretion of potassium	Baseline, week 4, week 8, week 12, week 16, week 20, week 24
Change in fractional urinary excretion of sodium	Change in fractional urinary excretion of sodium	Baseline, week 4, week 8, week 12, week 16, week 20, week 24
Change in fractional urinary excretion of chloride	Change in fractional urinary excretion of chloride	Baseline, week 4, week 8, week 12, week 16, week 20, week 24
Change in fractional urinary excretion of magnesium	Change in fractional urinary excretion of magnesium	Baseline, week 4, week 8, week 12, week 16, week 20, week 24
Change in urinary calcium/creatinine ratio	Change in urinary calcium/creatinine ratio	Baseline, week 4, week 8, week 12, week 16, week 20, week 24
Change in urinary excretion of renin	Change in urinary excretion of renin	Baseline, week 4, week 8, week 12, week 16, week 20, week 24
Change in urinary excretion of aldosterone	Change in urinary excretion of aldosterone	Baseline, week 4, week 8, week 12, week 16, week 20, week 24
Gitelman symptom questionnaire	With the Gitelman symptom questionnaire, symptoms can be scored for frequency of apperance and severity. This questionnaire also contains the 36-Item Short Form Health Survey (RAND SF-36) quality of life questionnaire	Baseline, week 4, week 8, week 12, week 16, week 20, week 24
Blood pressure (including orthostatic hypotension measurement)	Measurement of blood pressure including measurement of orthostatic blood pressure	Baseline, week 4, week 8, week 12, week 16, week 20, week 24
Weight	Body Weight	Baseline, week 4, week 8, week 12, week 16, week 20, week 24
Muscle strength	Muscle strength will be measured by hand grip dynamometer	Baseline, week 4, week 8, week 12, week 16, week 20, week 24

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Collaborators: Dutch Kidney Foundation
• Investigators: Principal Investigator: Tom Nijenhuis, MD PhD, Radboud University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): April 19, 2021
• Primary Completion (Actual): September 1, 2024
• Study Completion (Actual): September 1, 2024

Study Registration Dates

• First Submitted: July 18, 2021
• First Submitted That Met QC Criteria: July 29, 2021
• First Posted (Actual): August 9, 2021

Study Record Updates

• Last Update Posted (Estimated): November 21, 2024
• Last Update Submitted That Met QC Criteria: November 18, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Genetic Diseases, Inborn; Disease; Renal Tubular Transport, Inborn Errors; Syndrome; Gitelman Syndrome
• Other Study ID Numbers: NL72495.091.19

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No