Interaction Between a Calcimimetic Agent and the Renin Angiotensine Aldosterone System

The recruitment status of this study is unknown because the information has not been verified recently.
Verified January 2012 by Centre Hospitalier Universitaire Vaudois.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Swiss National Science Foundation
Information provided by (Responsible Party):
Michel Burnier, Centre Hospitalier Universitaire Vaudois
ClinicalTrials.gov Identifier:
NCT01519037
First received: January 24, 2012
Last updated: January 27, 2012
Last verified: January 2012
  Purpose

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.


Condition Intervention
Relationship Between Calcimimetic and the RAAS
Drug: calcimimetic agent (cinacalcet)
Drug: placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Evaluation of the Interaction Between a Calcimimetic Agent (Cinacalcet) and the Renin Angiotensine Aldosterone System in Healthy Volunteers

Resource links provided by NLM:


Further study details as provided by Centre Hospitalier Universitaire Vaudois:

Primary Outcome Measures:
  • Effect of cinacalcet compared to placebo on plasma renin activity [ Time Frame: up to 36 days ] [ Designated as safety issue: No ]
    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


Secondary Outcome Measures:
  • effect of cinacalcet administered as single dose (compared to placebo) on plasma aldosterone and on hemodynamics [ Time Frame: up to 36 days ] [ Designated as safety issue: No ]
    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).


Estimated Enrollment: 24
Study Start Date: January 2012
Estimated Study Completion Date: January 2013
Estimated Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Drug: calcimimetic agent (cinacalcet)
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
Drug: placebo
one dose of oral placebo

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.

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01519037

Contacts
Contact: Valentina Forni, MD +41 79 556 18 65 valentina.forni@chuv.ch

Locations
Switzerland
CHUV, service de néphrologie/hypertension Recruiting
Lausanne, Vaud, Switzerland, 1011
Contact: Valentina Forni, MD    +41 79 556 18 65    valentina.forni@chuv.ch   
Sub-Investigator: Valentina Forni, MD         
Sponsors and Collaborators
Centre Hospitalier Universitaire Vaudois
Swiss National Science Foundation
Investigators
Principal Investigator: Michel Burnier, Professor CHUV
  More Information

Publications:
Responsible Party: Michel Burnier, Professor, Centre Hospitalier Universitaire Vaudois
ClinicalTrials.gov Identifier: NCT01519037     History of Changes
Other Study ID Numbers: 2011DR4219
Study First Received: January 24, 2012
Last Updated: January 27, 2012
Health Authority: Switzerland: Swissmedic

Keywords provided by Centre Hospitalier Universitaire Vaudois:
calcimimetic agent
RAAS
renin
aldosterone

Additional relevant MeSH terms:
Calcimimetic Agents
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 14, 2014