Autosomal Dominant Polycystic Kidney Disease (ADPKD)Phase 2/3NCT02225860
Diet as a Potential Treatment for Autosomal Dominant Polycystic Kidney Disease
A Phase 2/3 study testing Diet and water adjustment in people with Autosomal Dominant Polycystic Kidney Disease (ADPKD), run by Tufts Medical Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Autosomal Dominant Polycystic Kidney Disease (ADPKD)
- What is being tested?
- Diet and water adjustment
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 1 siteUnited States
- Study dates
- May 2014to Feb 2016
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Low Osmolar Diet and Adjusted Water Intake for Vasopressin Suppression in ADPKD
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.
Read the 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.
- Being tested
- Diet and water adjustment
- Keywords
- ADPKD, Copeptin, Vasopressin, Diet, Water
- Medical subject headings
- Polycystic Kidney, Autosomal Dominant, Diabetes Insipidus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Diet and water adjustmentBehavioural
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
| Study group | Role | What they receive |
|---|---|---|
| Diet and Water adjustment | Active comparator | Reduction in dietary salt and protein intake Receives: Behavioral: Diet and water adjustment |
| Control | No intervention | Continue with usual diet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Mean Serum Copeptin From Baseline (a Reflection of Endogenous Vasopressin Production) at Week 2
The copeptin level will reflect the combined effect of low osmolar diet and adjusted water intake at week 2
Measured: Baseline to week 2
Secondary outcomes (2)
Change in Total Daily Urinary Solutes From 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.
Measured: Baseline to week 2
Change in Mean Serum Copeptin Level From Baseline to Week 1
Mean serum copeptin level at week one which will reflect the effect of low osmolar diet alone.
Measured: baseline to week 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Aug 2014 (estimated)
- Study startMay 2014
- Primary completionFeb 2016
- Study completionFeb 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Autosomal Dominant Polycystic Kidney Disease (ADPKD)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tufts Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ronald Perrone, MD, Principal investigator, Tufts Medical CenterOsama Amro, MD, Principal investigator, Tufts Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02225860
- Sponsor's protocol ID
- 11111
- Status last verified
- Feb 2017
- First submitted
- 20 Aug 2014
- Last updated
- 30 Mar 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
St Pierre K, Cashmore BA, Bolignano D, Zoccali C, Ruospo M, Craig JC, Strippoli GF, Mallett AJ, Green SC, Tunnicliffe DJ. Interventions for preventing the progression of autosomal dominant polycystic kidney disease. Cochrane Database Syst Rev. 2024 Oct 2;10(10):CD010294. doi: 10.1002/14651858.CD010294.pub3.
PubMed 39356039
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Low Osmolar Diet and Adjusted Water Intake for Vasopressin Suppression in ADPKD
- ClinicalTrials.gov ID
- NCT02225860
- Acronym / sponsor ID
- 11111
- Keywords
- ADPKD, Copeptin, Vasopressin, Diet, Water
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- Tufts Medical CenterUniversity, hospital or other
- Study start
- May 2014
- Primary completion
- Feb 2016 (actual)
- Study completion
- Feb 2016 (actual)
- First posted
- 26 Aug 2014 (estimated)
- Results
- Posted 30 Mar 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Diet and Water adjustment | Active comparator | Behavioral: Diet and water adjustmentReduction in dietary salt and protein intake |
| Control | No intervention | –Continue with usual diet |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Diet and water adjustmentThe 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 | Behavioural | Diet and Water adjustment |
Primary outcome
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
2 secondary outcomes
Change in Total Daily Urinary Solutes From Baseline to Week 2
Time frame: Baseline to week 2
Change in Mean Serum Copeptin Level From Baseline to Week 1
Time frame: baseline to week 1
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39356039St Pierre K, Cashmore BA, Bolignano D, Zoccali C, Ruospo M, Craig JC, Strippoli GF, Mallett AJ, Green SC, Tunnicliffe DJ. Interventions for preventing the progression of autosomal dominant polycystic kidney disease. Cochrane Database Syst Rev. 2024 Oct 2;10(10):CD010294. doi: 10.1002/14651858.CD010294.pub3.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ronald Perrone, MD principal investigator
Tufts Medical Center
Osama Amro, MD principal investigator
Tufts Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Diet and water adjustment in people with Autosomal Dominant Polycystic Kidney Disease (ADPKD), run by Tufts Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Mar 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Mean Serum Copeptin From Baseline (a Reflection of Endogenous Vasopressin Production) at Week 2 (time frame: Baseline to week 2). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02225860, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Mar 2017.