Interaction Between a Calcimimetic Agent and the Renin Angiotensine Aldosterone System

March 3, 2020 updated by: Michel Burnier, Centre Hospitalier Universitaire Vaudois

Evaluation of the Interaction Between a Calcimimetic Agent (Cinacalcet) and the Renin Angiotensine Aldosterone System in Healthy Volunteers

The aim of this study is to evaluate, in healthy volunteers, the acute modulating effect of cinacalcet on the RAAS, the effect of furosemide on parathyroid secretion of PTH and the interaction between furosemide and cinacalcet on parathyroid hormone secretion.

Study Overview

Detailed Description

The clinical trial will be monocentric (Service of Nephrology and Hypertension at CHUV, Lausanne) and will include 24 patients. The volunteers will get involved after inclusion (Inclusion Visit) in a crossover study over two double-blind periods. The order of the two periods (placebo or cinacalcet) will be randomized. Each period comprises 3 days of a low-sodium diet (50 mmol of Na+ per day, equivalent to 3 grams of salt/day), followed by an investigation day at the hospital during which the subjects will be studied before and after exposure to the cinacalcet or placebo. The 2 periods will be separated by a therapeutic wash-out lasting 14-28 days. The total length of the study per participant will be 1, max. 2 months.

Study Type

Interventional

Enrollment (Actual)

18

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Vaud
      • Lausanne, Vaud, Switzerland, 1011
        • CHUV, service de néphrologie/hypertension

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 45 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • Healthy subject
  • Male

    • Age > 18 and < 45 years old
    • Caucasian
    • Non-smoker
    • BMI >18 and < 25 Kg/m2
    • Normal clinical examination
    • ECG normal, 12 leads
    • Systolic arterial pressure (SBP) ≥100 ≤ 139 mmHg and diastolic arterial pressure (DBP) ≥50 ≤ 89 mmHg (after 5 minutes lying down, 3 measurements at 2-minute intervals; Omron machine; left arm)
    • Heart rate (HR) ≥ 45 ≤ 90 beats/min
    • Subject capable of understanding the written information and the written consent form.
    • Subject must have given written, dated and signed consent before starting any trial procedure.

Exclusion Criteria:

  • • Female

    • Age < 18 or > 45 years old
    • Electrolyte disturbances, defined as any sodium, potassium, total or ionized calcium, phosphate or magnesium value outside of the laboratory's reference values (at the Inclusion Visit).
    • Seropositive for HIV, HBV or HCV (at the Inclusion Visit).
    • Positive detection of drugs in urine (opiates, cannabinoids, cocaine, benzodiazepines, amphetamines or barbiturates) (at the Inclusion Visit).
    • Fall in SBP > or DBP > 10 mmHg after standing for 1 minute or any clinical manifestation of postural hypotension (at the Inclusion Visit).
    • Any history of diseases or clinically significant conditions which may be gastrointestinal (such as gastritis or gastric ulcer), respiratory, psychiatric, neurological (medical history of convulsions), renal, hepatic or cardiac or other diseases/conditions or abnormal physical signs which may interfere with the study's objectives. The investigator may disqualify any subject for a valid medical or psychiatric reason.
    • Ongoing involvement or in the 60 days prior to the Inclusion Visit in another research study.
    • Chronic use of any medication (prescribed or not) during the 4 weeks prior to the Inclusion Visit (only the use of medications such as paracetamol for headaches will be tolerated at the lowest dose possible.
    • Use of any medication known as CYP P450 3A4 inhibitors during the 12 weeks prior to the Inclusion Visit (amiodarone, diltiazem, verapamil, ketoconazole, itraconazole, voriconazole, posaconazole, fluconazole, miconazol, ritonavir, nelfinavir, amprenavir, indinavir, atazanavir, erythromycin, clarithromycin, josamycin, telithromycin)
    • Donation of blood, plasma and/or marrow in the 3 months prior to the Inclusion Visit
    • Medical history of dependence on drugs or alcohol abuse as defined by the DSM IVR, criteria for diagnosing drug and alcohol abuse and dependence on drugs.
    • Medical history of intolerant reactions to cinacalcet or furosemide (or derivatives of sulfamides)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: calcimimetic agent (cinacalcet)
3 days of a low-sodium diet (50 mmol of Na+ per day, equivalent to 3 grams of salt/day), followed by an investigation day at the hospital during which the subjects will be studied before and after exposure to the cinacalcet or the placebo. The 2 periods will be separated by a therapeutic wash-out lasting 14-28 days. The total length of the study per participant will be 1, max. 2 months
one dose of oral cinacalcet, 60mg
Placebo Comparator: Placebo
3 days of a low-sodium diet (50 mmol of Na+ per day, equivalent to 3 grams of salt/day), followed by an investigation day at the hospital during which the subjects will be studied before and after exposure to the cinacalcet or placebo. The 2 periods will be separated by a therapeutic wash-out lasting 14-28 days. The total length of the study per participant will be 1, max. 2 months
one tablet of placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Effect of cinacalcet compared to placebo on plasma renin activity
Time Frame: up to 36 days
to determine the acute effect of a single high dose of cinacalcet compared to placebo on plasma renin activity (PRA), under RAAS-stimulating conditions (low sodium diet, furosemide injection) by PRA plasma measure
up to 36 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
effect of cinacalcet administered as single dose (compared to placebo) on plasma aldosterone and on hemodynamics
Time Frame: up to 36 days
to determine the effect of cinacalcet administered as single dose (compared to placebo) on plasma aldosterone and on hemodynamics (blood pressure, heart rate), under RAAS stimulating conditions (low sodium diet, furosemide injection).
up to 36 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Michel Burnier, Professor, CHUV

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2012

Primary Completion (Actual)

June 1, 2012

Study Completion (Actual)

June 1, 2014

Study Registration Dates

First Submitted

January 24, 2012

First Submitted That Met QC Criteria

January 24, 2012

First Posted (Estimate)

January 26, 2012

Study Record Updates

Last Update Posted (Actual)

March 5, 2020

Last Update Submitted That Met QC Criteria

March 3, 2020

Last Verified

March 1, 2020

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Publication

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.

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