A Translational Approach to Gitelman Syndrome
Condition: Gitelman Syndrome
MeSH terms: Gitelman Syndrome; Syndrome
Study type: Interventional

Summary: 
      This study will test the response to a single dose of thiazide diuretic as a diagnostic test
      for Gitelman syndrome. Individuals with hypokalemic alkalosis will be enrolled. After a
      baseline study, they will have the response to 50 mg hydrochlorothiazide on fractional
      chloride excretion examined.
    

Detailed description: 
      The purpose of this study is to test the hypothesis that Gitelman syndrome (GS) can be
      diagnosed using a simple clinical protocol. GS is an inherited kidney disease that usually
      shows up in patients as low blood potassium levels. Currently, no commercial genetic test for
      GS exists. Currently, GS is diagnosed based upon clinical findings but this method is not
      precise and often not reliable. Thus, in order to develop new treatments specific for GS
      patients, a more exact method of diagnosis would be of benefit.

      Eligible subjects are men and women ages 21-60 with normal blood pressure who have been
      diagnosed with low blood potassium of uncertain cause. Subjects may withdraw at any time.

      This study requires 3 visits to OHSU's campus. Study Visit 1 will occur during a normal visit
      with the nephrologist. As part of the normal visit, a complete interview, physical exam and
      urine and blood samples will be taken. In addition, another blood sample will be taken and
      used for genetic analysis. A urine pregnancy test will be administered. A Quality of Life
      survey, described below, will be administered. The genetic analysis, urine pregnancy test and
      Quality of Life survey are not normal tests for GS. Blood and urine samples, as well as
      pregnancy tests will be collected/administered at the Oregon Clinical and Translational
      Research Institute (OCTRI).

      During the intervention period, subjects will refrain from taking their potassium sparing
      medications for 7 days. This period is called the washout period and is needed to ensure that
      blood tests during the hydrochlorthiazide (HCTZ, a "water pill") (see below), are not
      affected by medications. On the 3rd day of the washout period, Study Visit 2 will occur at
      the OCTRI. This will require blood to be drawn, to insure that subjects maintain proper blood
      levels of potassium and magnesium. Magnesium and potassium supplements will be allowed during
      the washout. After review of the blood test results, the investigator may adjust the doses of
      these supplements in order to keep subject blood levels of potassium and magnesium as close
      to normal as possible. Blood pressure, heart rate and breathing rate will also be checked at
      this visit.

      Study Visit 3 will occur at the OCTRI and will be devoted to the HCTZ test. During the course
      of the HCTZ test, subjects will have an plastic tube (an IV) placed in an arm vein, have
      vital signs checked and receive 50mg of HCTZ to take by mouth . Subjects will provide 8 urine
      samples and 3 blood samples. The time required for this visit is expected to be 6 hours.

      The total time required for subjects to complete the study from Study Visit 1 through
      discharge from the OCTRI on Study Visit 3 will not be less than 9 days and subjects should
      not expect the total length to exceed three weeks depending on available appointments for
      Study Visit 3 at the OCTRI.

      The Quality of Life survey is derived from a national research corporation and has been
      modified for use in this study. The authors of this survey allow free public use of this
      document provided it is properly referenced in any presentation of the study's results.

      HCTZ is an FDA approved medication. There are no experimental drugs or devices used in this
      study.

      The purpose of this study is to develop methods for, and determine the feasibility of,
      performing a HCTZ test and genetic analysis for GS at OHSU. There is no statistical analysis
      of data, but descriptive characteristics will be entered into an Access database with
      password restricted access. Genetic samples will be analyzed using PCR and standard
      sequencing techniques. Data and samples will be stored for a maximum of 15 years.
    

Intervention name(s): Hydrochlorothiazide
Intervention type(s): Drug
Intervention description(s): 50 mg one time
Other intervention name(s): HCTZ
Intervention MeSH terms: Hydrochlorothiazide
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: Hypokalemia; Bartter Syndrome; Salt Wasting