Salt Supplementation in Gitelman Syndrome

Study Overview
=================
Brief Summary
-----------------
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.

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.

Official Title
-----------------
Exploratory Study Into the Effect of Salt Supplementation in Gitelman Syndrome

Conditions
-----------------
Gitelman Syndrome

Intervention / Treatment
-----------------
* Dietary Supplement: Salt (NaCl)
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 16 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Single subject multiple randomized double-blinded multi-crossover placebo-controlled trials (N-of-1 trials)
Masking: Quadruple


Arms and Interventions

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

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 |