- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02225860
Diet as a Potential Treatment for Autosomal Dominant Polycystic Kidney Disease
Low Osmolar Diet and Adjusted Water Intake for Vasopressin Suppression in ADPKD
Study Overview
Status
Intervention / Treatment
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 Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 3
Contacts and Locations
Study Locations
-
-
Massachusetts
-
Boston, Massachusetts, United States, 02111
- Tufts Medical Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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:
- Patients on chronic use of medications known to affect AVP secretion (Serotonin Specific Reuptake inhibitors (SSRI), Opioids, Tricyclic Antidepressants (TCA) and Tolvaptan)
- 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.
- Baseline hyponatremia (Na below 135 mEq/l)
- Inability to comply with dietary or fluid requirements
- Have physical or cognitive impairments which prevent participation
- Pregnant women
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Diet and Water adjustment
Reduction in dietary salt and protein intake
|
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
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
Baseline to week 2
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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. |
Baseline to week 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.
|
baseline to week 1
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Ronald Perrone, MD, Tufts Medical Center
- Principal Investigator: Osama Amro, MD, Tufts Medical Center
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 11111 (DAIDS ES Registry Number)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Autosomal Dominant Polycystic Kidney Disease (ADPKD)
-
University of North Carolina, Chapel HillNational Institute of General Medical Sciences (NIGMS)CompletedRenal Disease | Autosomal Dominant Polycystic Kidney Disease | ADPKDUnited States
-
Kadmon Corporation, LLCTerminatedAutosomal Dominant Polycystic Kidney Disease (ADPKD)United States
-
Assistance Publique - Hôpitaux de ParisIPSEN pharmaceutical company, Boulogne-Billancourt, FranceCompletedAutosomal Dominant Polycystic Kidney Disease (ADPKDFrance
-
University Medical Center GroningenRadboud University Medical Center; Erasmus Medical Center; Leiden University...UnknownAutosomal Dominant Polycystic Kidney Disease (ADPKD)Netherlands
-
Mario Negri Institute for Pharmacological ResearchCompletedAutosomal Dominant Polycystic Kidney Disease (ADPKD)Italy
-
Palladio BiosciencesCentessa Pharmaceuticals plcTerminatedADPKD | Polycystic Kidney Disease, AdultUnited States
-
Children's National Research InstituteRecruiting
-
Vertex Pharmaceuticals IncorporatedNot yet recruitingAutosomal Dominant Polycystic Kidney Disease (ADPKD)
-
University of CologneRecruitingADPKD (Autosomal Dominant Polycystic Kidney Disease)Germany
-
University of ZurichCompletedAutosomal Dominant Polycystic Kidney Disease (ADPKD)Switzerland
Clinical Trials on Diet and water adjustment
-
University of GiessenCompletedDeglutition Disorders | Dysphagia | Aspiration Pneumonia | Intensive Care Neurological DisorderGermany
-
University of California, BerkeleyCompleted
-
Virginia Polytechnic Institute and State UniversityRecruiting
-
University of California, IrvineNational Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); University...CompletedType 2 DiabetesUnited States
-
University of ParmaUnknownHypertension | Obesity | Overweight | Urinary StonesItaly
-
Second Affiliated Hospital, School of Medicine,...Recruiting
-
University of CologneCompleted
-
George Washington UniversityCompletedObesity | Diabetes
-
Centro Hospitalar do Baixo VougaCompleted
-
Samsung Medical CenterCompletedBrain Surgery With Motor Evoked Potential Monitoring | Spine Surgery With Motor Evoked Potential MonitoringKorea, Republic of