POLY: Effect of Tolvaptan on Renal Plasma Flow (RPF) and Glomerular Filtration Rate (GFR) in ADPKD

• Sponsor: Regional Hospital Holstebro (Other)
• Overall Status: Completed
• CT.gov ID: NCT03803124
• Collaborator: (none)
• Enrollment: 20
• Location: 1
• Arms: 2
• Actual Duration (Months): 24.5
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

Polycystic kidney disease (ADPKD) is a common genetic disorder, characterized by the formation of cysts in the kidneys, causing gradual renal function-loss. Previous studies have shown that, reduced glomerular filtration rate (GFR) and renal plasma flow (RPF) play a role in the progression of renal disease in ADPKD. Tolvaptan is a vasopressin 2 antagonist, which seems to reduce the growth of total kidney volume (TKV) and the decline in e-GFR in ADPKD. The mechanism is not fully understood and could, at least partly, be caused by stimulation of the renal blood flow. The purpose of this trial is to investigate if tolvaptan´s improve renal blood flow and glomerular filtration in ADPKD, in a randomized, cross-over, double-blind, placebo-controlled study.

Condition or Disease	Intervention/Treatment	Phase
Polycystic Kidney, Autosomal Dominant	Drug: Tolvaptan; Drug: Placebo	Phase 3

Detailed Description

The aim is to measure the acute effects of tolvaptan on:

1. Renal hemodynamics (RPF, GFR, filtration fraction ((FF)) and renovascular resistance ((RVR))

2. Blood pressure (central blood pressure ((cBP)) and brachial blood pressure bBP)

3. Several vasoactive hormones (plasma renin ((PRC)), plasma angiotensin II ((p-Ang-II)), plasma aldosterone ((p-Aldo)), plasma vasopressin ((p-AVP))

in patients with ADPKD.

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Basic Science
• Official Title: Effect of Tolvaptan on Renal Plasma Flow (RPF) and Glomerular Filtration Rate (GFR) in ADPKD
• Actual Study Start Date: Dec 1, 2015
• Actual Primary Completion Date: Dec 15, 2017
• Actual Study Completion Date: Dec 15, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Tolvaptan Drug: Tolvaptan 1 tablet before renography	Drug: Tolvaptan; 1 tablet before renography
Placebo Comparator: Placebo Placebo 1 tablet before renography	Drug: Placebo; 1 tablet before renography

Outcome Measures

Primary Outcome Measures

1. Renal plasma flow (RPF) [Two hours after trial medicine intake]

   Estimated by posterior Technetium-99m diethylenetriamine penta-acetic acid (99-mTc-DTPA) renography 2 hours after trial medicine intake. (unit of measurement= ml/min)

Secondary Outcome Measures

1. Central and brachial blood pressures (BP) [Measured every 15 minutes during the examination day]

   Measured using Mobil-O-Graph® PWA (unit of measurement= mmHg)

2. Glomerular filtration rate (GFR) [Two hours after trial medicine intake]

   Estimated by posterior Technetium-99m diethylenetriamine penta-acetic acid (99-mTc-DTPA) renography 2 hours after trial medicine intake. (unit of measurement= ml/min)

3. Filtration fraction (FF) [Two hours after trial medicine intake]

   Estimated by posterior Technetium-99m diethylenetriamine penta-acetic acid (99-mTc-DTPA) renography 2 hours after trial medicine intake. (unit of measurement= %)

4. Plasma concentration of vasopressin (p-AVP) [Measured before and 3 hours after trial medicine intake]

   Blood samples (unit of measurement= pg/ml)

5. Plasma concentration of aldosterone (p-Aldo) [Measured before and 3 hours after trial medicine intake]

   Blood samples (unit of measurement= pmol/ml)

6. Plasma concentration of angiotensin II (p-AngII) [Measured before and 3 hours after trial medicine intake]

   Blood samples (unit of measurement= pg/ml)

7. Plasma concentration of renin (PRC) [Measured before and 3 hours after trial medicine intake]

   Blood samples (unit of measurement= pg/ml)

8. Urine excretion of aquaporin 2 (u-AQP2) [Measured before and 3 hours after trial medicine intake]

   Urine sample (unit of measurement= ng/ml)

9. Urine output (OU) [Measured before and 3 hours after trial medicine intake]

   Urine sample (unit of measurement= ml/min)

10. Urine osmolality (U-osm) [measured before and 3 hours after trial medicine intake]

    Urine sample (unit of measurement= mosmol/kg)

11. Fractional excretion of sodium (FENa) [Measured before and 3 hours after trial medicine intake]

    Blood and urine sample (unit of measurement= %)

12. Albumin excretion rate [Measured before and 3 hours after trial medicine intake]

    Blood and urine sample (unit of measurement= mg/min)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age > 18 years

• Diagnosis with ADPKD

• Informed consent

• Contraception for fertile women

Exclusion Criteria:

• Renal transplantation

• Operation in the kidney

• Diabetes mellitus

• Neoplastic conditions

• Pregnancy, nursing

• Unwillingness to participate

• eGFR > 30

• Intolerance towards tolvaptan

• Alcohol or medical abuse,

• BP >>170/110 blood pressure despite regulation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Departments of medical research and medicine	Holstebro		Denmark	7500

Sponsors and Collaborators

• Regional Hospital Holstebro

Investigators

• Principal Investigator: Frank Mose, MD, Ph D, Departments of medical research and medicine

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Erling Bjerregaard Pedersen, Professor, Regional Hospital Holstebro
• ClinicalTrials.gov Identifier: NCT03803124
• Other Study ID Numbers: FHM-1-2015
• First Posted: Jan 14, 2019
• Last Update Posted: Jan 14, 2019
• Last Verified: Jan 1, 2019

• Keywords provided by Erling Bjerregaard Pedersen, Professor, Regional Hospital Holstebro: CYSTS, KIDNEYS
• Additional relevant MeSH terms: Polycystic Kidney Diseases; Polycystic Kidney, Autosomal Dominant; Tolvaptan

Study Results

No Results Posted as of Jan 14, 2019