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Diet as a Potential Treatment for Autosomal Dominant Polycystic Kidney Disease

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ClinicalTrials.gov Identifier: NCT02225860
Recruitment Status : Completed
First Posted : August 26, 2014
Results First Posted : March 30, 2017
Last Update Posted : March 30, 2017
Sponsor:
Information provided by (Responsible Party):
Tufts Medical Center

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.

Condition or disease Intervention/treatment Phase
Autosomal Dominant Polycystic Kidney Disease (ADPKD) Behavioral: Diet and water adjustment Phase 2 Phase 3

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 34 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Low Osmolar Diet and Adjusted Water Intake for Vasopressin Suppression in ADPKD
Study Start Date : May 2014
Actual Primary Completion Date : February 2016
Actual Study Completion Date : February 2016

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Diet and Water adjustment
Reduction in dietary salt and protein intake
Behavioral: Diet and water adjustment
The dietary intervention consisted of three elements: low sodium (1500 mg/day), low protein (daily protein dietary allowance of 0.8 gram/kg body weight), and low urea (avoidance of preservatives, food additives, bulking agents, and chewing gum). Protein was factored by measured body weight to mirror the estimated average requirement (EAR) of healthy adults which is set on a grams per kilogram basis

No Intervention: Control
Continue with usual diet



Primary Outcome Measures :
  1. Change in Mean Serum Copeptin From Baseline (a Reflection of Endogenous Vasopressin Production) at Week 2 [ Time Frame: Baseline to week 2 ]
    The copeptin level will reflect the combined effect of low osmolar diet and adjusted water intake at week 2


Secondary Outcome Measures :
  1. Change in Total Daily Urinary Solutes From Baseline to Week 2 [ Time Frame: Baseline to week 2 ]

    Total daily urinary solutes (this will serve as a surrogate for diet adherence and is known to be associated with lower vasopressin secretion).

    Total daily solutes is the total amount of osmoles detected in 24 hours urine collection.


  2. Change in Mean Serum Copeptin Level From Baseline to Week 1 [ Time Frame: baseline to week 1 ]
    Mean serum copeptin level at week one which will reflect the effect of low osmolar diet alone.



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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02225860


Locations
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United States, Massachusetts
Tufts Medical Center
Boston, Massachusetts, United States, 02111
Sponsors and Collaborators
Tufts Medical Center
Investigators
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Principal Investigator: Ronald Perrone, MD Tufts Medical Center
Principal Investigator: Osama Amro, MD Tufts Medical Center

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Responsible Party: Tufts Medical Center
ClinicalTrials.gov Identifier: NCT02225860     History of Changes
Other Study ID Numbers: 11111
First Posted: August 26, 2014    Key Record Dates
Results First Posted: March 30, 2017
Last Update Posted: March 30, 2017
Last Verified: February 2017
Keywords provided by Tufts Medical Center:
ADPKD
Copeptin
Vasopressin
Diet
Water
Additional relevant MeSH terms:
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Kidney Diseases
Polycystic Kidney Diseases
Polycystic Kidney, Autosomal Dominant
Urologic Diseases
Kidney Diseases, Cystic
Abnormalities, Multiple
Congenital Abnormalities
Ciliopathies
Genetic Diseases, Inborn
Vasopressins
Hemostatics
Coagulants
Vasoconstrictor Agents
Antidiuretic Agents
Natriuretic Agents
Physiological Effects of Drugs