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Treatment of Vascular Stiffness in ADPKD (TRAMPOLINE)

Primary Purpose

Autosomal Dominant Polycystic Kidney

Status
Recruiting
Phase
Phase 4
Locations
Netherlands
Study Type
Interventional
Intervention
Sodium chloride (NaCl)
Placebo
Amiloride Hcl 5mg Tab
Sponsored by
Erasmus Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Autosomal Dominant Polycystic Kidney focused on measuring Polycystic kidney disease, Amiloride, Salt, Hypertension

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Adults with typical ADPKD diagnosed based on Ravine criteria and/or a documented Pkd 1 or 2 mutation
  • Chronic kidney disease epidemiology collaboration equation estimated glomerular filtration rate ≥60 ml/min/1.73m2
  • Ability to provide informed consent

Exclusion Criteria:

  • Uncontrolled hypertension, defined as an office blood pressure of ≥160/ ≥90 mmHg with or without antihypertensive treatment
  • Concomitant use of ≥ 3 antihypertensive medications
  • When antihypertensive treatment is prescribed for any other treatment indication than hypertension (e.g. cardia arrhythmia)
  • Serum potassium levels >5.5 mmol/L (measured within last 6 months)
  • History of liver disease (excluding liver cysts due to ADPKD)
  • History of heart failure (cardiac ejection fraction < 35%) or cardiac arrhythmia
  • History of diabetes mellitus
  • Active infection or antibiotic therapy
  • Immunosuppressive therapy within the last year
  • Concomitant use of drugs that could influence blood pressure and/or disease progression (Tolvaptan/non-steroidal anti-inflammatory drugs (NSAIDs)/chemotherapy), excluding < 3 antihypertensive drugs
  • Actual pregnancy or unwillingness to adhere to reproductive precautions during the duration of the study

Sites / Locations

  • Erasmus University Medical Centre RotterdamRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

High-salt group (group 1)

Low-salt group (group 2)

Arm Description

All participants will be subjected to a low-salt diet (3.5 grams/day) for six weeks. Group 1 will receive sodium chloride capsules (6 grams/day) for four weeks. In the last two weeks of the trial, all participants will be treated with amiloride tablets (20 mg daily) in open-label setting.

All participants will be subjected to a low-salt diet (3.5 grams/day) for six weeks. Group 2 will receive placebo capsules (6 grams/day) for four weeks. In the last two weeks of the trial, all participants will be treated with amiloride tablets (20 mg daily) in open-label setting.

Outcomes

Primary Outcome Measures

Arterial stiffness induced by high salt diet
Difference in central arterial stiffness, measured as the pulse wave velocity (PWV), in high-salt group versus low-salt group.
Effect of treatment with amiloride on arterial stiffness in high-salt group
Difference in central arterial stiffness, measured as the pulse wave velocity (PWV), before versus after amiloride treatment in high-salt group.
Effect of treatment with amiloride on arterial stiffness in low-salt group
Difference in central arterial stiffness, measured as the pulse wave velocity (PWV), before versus after amiloride treatment in low-salt group.

Secondary Outcome Measures

Blood pressure
24-hours ambulatory blood pressure measurement (Mobil-O-Graph).
Salt tasting thresholds
Sodium chloride (NaCl) solutions with different concentrations to assess the salt tasting thresholds.
Skin sodium accumulation
In a subgroup of participants, tissue sodium concentration (23Na) will be assessed noninvasively using a contrast-free 23 Na-MRI scan.
Markers of (vascular) inflammation and endothelial dysfunction
Blood biomaterials will be collected at the visits. We will measure inflammatory markers including the high-sensitivity C-reactive protein, interleukin-6 and tumor necrosis factor-α, and other relevant markers for endothelial dysfunction including the adhesion molecules intercellular cell adhesion molecules-1, vascular cell adhesion molecules-1 and endothelin-1.

Full Information

First Posted
January 12, 2022
Last Updated
September 6, 2023
Sponsor
Erasmus Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT05228574
Brief Title
Treatment of Vascular Stiffness in ADPKD
Acronym
TRAMPOLINE
Official Title
Treatment of Vascular Stiffness in Patients With Autosomal Dominant Polycystic Kidney Disease
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 11, 2022 (Actual)
Primary Completion Date
December 31, 2024 (Anticipated)
Study Completion Date
December 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Erasmus Medical Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease characterized by cystic kidneys and caused by mutations in the polycystic kidney disease and other rare genes. It is associated with salt-sensitive hypertension, which accounts for the majority of morbidity and mortality. About 70% of patients with ADPKD develop hypertension, prior to the onset of kidney function decline. Early onset hypertension, despite its treatment, is independently associated with rapid kidney function decline. The investigators hypothesize that a high-sodium diet in patients with ADPKD is required for the development of vascular stiffness, which precedes hypertension, and that treatment with amiloride reverses this phenomenon.
Detailed Description
Objective of the study: The investigators aim to investigate if arterial stiffness is exacerbated due to a high-salt diet in patients with ADPKD. The investigators also aim to explore whether treatment with amiloride prevents the arterial stiffness caused by a high-salt diet. Study design: Randomized, double blinded and placebo-controlled clinical trial with open-label treatment with amiloride Study population: Adults with ADPKD with an estimated glomerular filtration rate (CKD-EPI) of ≥ 60 ml/min/1.73m2 Intervention: All participants will be subjected to a low-salt diet (3,5 grams/day) throughout the study for a total of 6 weeks. After a run-in period of 2 weeks, participants will be randomized into two treatment groups: Group 1: Sodium chloride capsules (6 grams/day) for 2 weeks, combined with amiloride (20 mg/day) in last 2 weeks Group 2: Placebo capsules for 2 weeks, combined with amiloride (20 mg/day) in last 2 weeks. Primary study parameters/outcome of the study: The three primary outcomes of this study are a difference in central arterial stiffness (pulse wave velocity, PWV) between: The high-salt group versus low-salt group; The high-salt group: before versus after amiloride treatment; The low-salt group: before versus after amiloride treatment. The burden of participation includes: A dietary salt restriction of 3.5 grams/day for a total period of 6 weeks Salt supplementation or placebo for a total period of 4 weeks Drug intervention with amiloride during the last 2 weeks Hospital visits

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Autosomal Dominant Polycystic Kidney
Keywords
Polycystic kidney disease, Amiloride, Salt, Hypertension

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
This is a single-centre, randomized, double-blinded, and placebo-controlled clinical trial with a secondary open-label part.
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
54 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
High-salt group (group 1)
Arm Type
Active Comparator
Arm Description
All participants will be subjected to a low-salt diet (3.5 grams/day) for six weeks. Group 1 will receive sodium chloride capsules (6 grams/day) for four weeks. In the last two weeks of the trial, all participants will be treated with amiloride tablets (20 mg daily) in open-label setting.
Arm Title
Low-salt group (group 2)
Arm Type
Placebo Comparator
Arm Description
All participants will be subjected to a low-salt diet (3.5 grams/day) for six weeks. Group 2 will receive placebo capsules (6 grams/day) for four weeks. In the last two weeks of the trial, all participants will be treated with amiloride tablets (20 mg daily) in open-label setting.
Intervention Type
Dietary Supplement
Intervention Name(s)
Sodium chloride (NaCl)
Other Intervention Name(s)
Table salt
Intervention Description
Sodium chloride capsules 6 grams per day for 4 weeks.
Intervention Type
Dietary Supplement
Intervention Name(s)
Placebo
Intervention Description
Placebo capsules, 6 grams per day for 4 weeks.
Intervention Type
Drug
Intervention Name(s)
Amiloride Hcl 5mg Tab
Other Intervention Name(s)
Amiloride
Intervention Description
Amiloride 5mg tablets, 20 mg per day for two weeks in open-label setting.
Primary Outcome Measure Information:
Title
Arterial stiffness induced by high salt diet
Description
Difference in central arterial stiffness, measured as the pulse wave velocity (PWV), in high-salt group versus low-salt group.
Time Frame
At week 3, week 5
Title
Effect of treatment with amiloride on arterial stiffness in high-salt group
Description
Difference in central arterial stiffness, measured as the pulse wave velocity (PWV), before versus after amiloride treatment in high-salt group.
Time Frame
At week 5 and at week 7
Title
Effect of treatment with amiloride on arterial stiffness in low-salt group
Description
Difference in central arterial stiffness, measured as the pulse wave velocity (PWV), before versus after amiloride treatment in low-salt group.
Time Frame
At week 5 and at week 7
Secondary Outcome Measure Information:
Title
Blood pressure
Description
24-hours ambulatory blood pressure measurement (Mobil-O-Graph).
Time Frame
At week 3, week 5 and at at week 7
Title
Salt tasting thresholds
Description
Sodium chloride (NaCl) solutions with different concentrations to assess the salt tasting thresholds.
Time Frame
At inclusion, week 3, week 5 and at week 7
Title
Skin sodium accumulation
Description
In a subgroup of participants, tissue sodium concentration (23Na) will be assessed noninvasively using a contrast-free 23 Na-MRI scan.
Time Frame
At week 3, week 5 and at week 7
Title
Markers of (vascular) inflammation and endothelial dysfunction
Description
Blood biomaterials will be collected at the visits. We will measure inflammatory markers including the high-sensitivity C-reactive protein, interleukin-6 and tumor necrosis factor-α, and other relevant markers for endothelial dysfunction including the adhesion molecules intercellular cell adhesion molecules-1, vascular cell adhesion molecules-1 and endothelin-1.
Time Frame
At inclusion, week 3, week 5 and at week 7

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Adults with typical ADPKD diagnosed based on Ravine criteria and/or a documented Pkd 1 or 2 mutation Chronic kidney disease epidemiology collaboration equation estimated glomerular filtration rate ≥60 ml/min/1.73m2 Ability to provide informed consent Exclusion Criteria: Uncontrolled hypertension, defined as an office blood pressure of ≥160/ ≥90 mmHg with or without antihypertensive treatment Concomitant use of ≥ 3 antihypertensive medications When antihypertensive treatment is prescribed for any other treatment indication than hypertension (e.g. cardia arrhythmia) Serum potassium levels >5.5 mmol/L (measured within last 6 months) History of liver disease (excluding liver cysts due to ADPKD) History of heart failure (cardiac ejection fraction < 35%) or cardiac arrhythmia History of diabetes mellitus Active infection or antibiotic therapy Immunosuppressive therapy within the last year Concomitant use of drugs that could influence blood pressure and/or disease progression (Tolvaptan/non-steroidal anti-inflammatory drugs (NSAIDs)/chemotherapy), excluding < 3 antihypertensive drugs Actual pregnancy or unwillingness to adhere to reproductive precautions during the duration of the study
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
L. Xue, MSc
Phone
(0031)107040704
Email
l.xue@erasmusmc.nl
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
M. Salih, MD, PhD
Organizational Affiliation
Erasmus Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Erasmus University Medical Centre Rotterdam
City
Rotterdam
State/Province
South-Holland
ZIP/Postal Code
3015GD
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
L. Xue, MSc
Phone
003130906182
Email
l.xue@erasmusmc.nl
First Name & Middle Initial & Last Name & Degree
M. Salih, MD, PhD

12. IPD Sharing Statement

Plan to Share IPD
No

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Treatment of Vascular Stiffness in ADPKD

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