Diet as a Potential Treatment for Autosomal Dominant Polycystic Kidney Disease

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Brief Title

Diet as a Potential Treatment for Autosomal Dominant Polycystic Kidney Disease

Official Title

Low Osmolar Diet and Adjusted Water Intake for Vasopressin Suppression in ADPKD

Brief Summary

      The purpose of this study is to learn if dietary habits can affect vasopressin secretion in
      patients with autosomal dominant polycystic kidney disease. Vasopressin increases the growth
      of kidney cysts and accelerates disease progression. Understanding how to control secretion
      of this hormone based on dietary habits may help to develop treatments to control this
      disease. The study will include about 60 patients from Tufts Medical Center. The study will
      last for 2 weeks. Blood and urine tests will be done 3 times during the study period.
      Subjects will be randomly assigned (by chance like flipping a coin), to one of two study
      groups. Group 1 will be given instructions to adjust their diet. This will include adjusting
      the amount of water, protein, and salt intake. Group 2 will have no adjustment of diet or
      water. The project has tremendous public health relevance, given the large numbers of people
      affected by autosomal dominant polycystic kidney disease and the substantial impact of the
      disease on morbidity, mortality, hospitalizations,dialysis or transplant, and societal costs
      of caring for those patients.
    

Detailed Description

      Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney
      disease with an estimated 600,000 persons affected in the United States and 12.5 million
      persons worldwide. To date, no disease-modifying treatment has been approved for the
      treatment of ADPKD.

      Arginine vasopressin (AVP) is a key player in cyst enlargement and disease progression. It
      has been established that patients with ADPKD have higher levels of AVP as compared to
      healthy controls. Suppression, blockade or elimination of AVP slows cyst progression. AVP-V2
      receptor inhibition controls disease progression in both animal models and humans, as does
      genetic elimination of vasopressin in the Polycystic Kidney (PCK) rat. This evidence
      indicates that AVP could be a promising target for therapeutic intervention. Unfortunately,
      the only clinically tested medication that blocks the AVP-V2 receptor (Tolvaptan) is
      associated with side effects including hypernatremia, hyperuricemia and elevated liver
      enzymes. An ideal therapeutic approach to target AVP in patients with ADPKD would be safe,
      easy to administer and could be adopted early in the disease process to prevent permanent
      kidney damage. High fluid intake presents one such possible treatment, and has been shown to
      suppress plasma levels of AVP, and slow cyst progression in an animal model of polycystic
      kidney disease. However, adherence to a high fluid intake diet is difficult to maintain in
      clinical practice.

      To address this adherence challenge, The investigators have developed a stepwise approach of
      combining a low osmolar diet (low protein and salt) with adjusted water intake, with the goal
      of lowering the amount of water intake needed to suppress AVP secretion. The major objective
      of this proposal is to evaluate whether this intervention can suppress vasopressin secretion
      in patients with early ADPKD. Vasopressin suppression will be assessed by measuring copeptin
      levels, which have been shown to be a reliable surrogate marker for the circulating AVP
      concentration.

      The rationale for this proposal is based on the fact that part of the difficulty in
      sustaining a low AVP level with daily water ingestion is the consumption of a diet that
      generates a large number of osmoles; high osmolar load stimulates vasopressin secretion to
      maintain water homeostasis. Hence, combining a low osmolar diet with adjusted water intake
      might prove to be sufficient to suppress vasopressin secretion in the clinical setting. The
      investigators propose the following:

      Specific Aim: To conduct a randomized controlled trial to evaluate the effect of a low
      osmolar diet and high water intake intervention on vasopressin secretion, urine osmolality,
      and daily solute excretion in adult patients with ADPKD. The investigators hypothesize that a
      low osmolar diet combined with adjusted water intake will decrease serum copeptin level and
      total daily solute excretion in patients with ADPKD as compared to the control arm.

      To accomplish the research goals, the current proposal builds upon existing expertise at
      Tufts Medical Center in conducting controlled clinical trials in patients with ADPKD.

      The expected outcomes include the identification of a relevant, safe, easily tolerated and
      affordable intervention that can suppress vasopressin secretion in ADPKD patients early in
      the disease process; the proposed stepwise approach of combining a low osmolar diet and
      adjusted water intake carries the premise of lowering the amount of water needed to suppress
      AVP secretion and potentially slow the progression of this devastating disorder.

      The study long-term goal is to evaluate whether this therapeutic approach could be tolerated
      by patients over a longer period of time, and could impact clinical outcome measures such as
      kidney volume and kidney function progression.
    

Study Phase

Phase 2/Phase 3

Study Type

Interventional


Primary Outcome

Change in Mean Serum Copeptin From Baseline (a Reflection of Endogenous Vasopressin Production) at Week 2

Secondary Outcome

 Change in Total Daily Urinary Solutes From Baseline to Week 2

Condition

Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Intervention

Diet and water adjustment

Study Arms / Comparison Groups

 Diet and Water adjustment
Description:  Reduction in dietary salt and protein intake

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Behavioral

Estimated Enrollment

34

Start Date

May 2014

Completion Date

February 2016

Primary Completion Date

February 2016

Eligibility Criteria

        Inclusion Criteria:

          -  Adults 18 to 60 years of age, who have ADPKD with an estimated glomerular filtration
             rate (eGFR) of 60 ml/min/1.73m2 or above

        Exclusion Criteria:

          1. Patients on chronic use of medications known to affect AVP secretion (Serotonin
             Specific Reuptake inhibitors (SSRI), Opioids, Tricyclic Antidepressants (TCA) and
             Tolvaptan)

          2. History of diseases influencing renal concentration capacity, such as, diabetes
             insipidus, adrenal or thyroid deficiencies, present or prior use of lithium, or kidney
             diseases other than ADPKD.

          3. Baseline hyponatremia (Na below 135 mEq/l)

          4. Inability to comply with dietary or fluid requirements

          5. Have physical or cognitive impairments which prevent participation

          6. Pregnant women
      

Gender

All

Ages

18 Years - 60 Years

Accepts Healthy Volunteers

No

Contacts

Ronald Perrone, MD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT02225860

Organization ID

11111


Responsible Party

Sponsor

Study Sponsor

Tufts Medical Center


Study Sponsor

Ronald Perrone, MD, Principal Investigator, Tufts Medical Center


Verification Date

February 2017