Interaction Between a Calcimimetic Agent and the Renin Angiotensine Aldosterone System

Sponsor

Centre Hospitalier Universitaire Vaudois (Other)

Overall Status

Completed

CT.gov ID

NCT01519037

Collaborator

Swiss National Science Foundation (Other)

Enrollment

Location

Arms

Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Relationship Between Calcimimetic and the RAAS	Drug: Cinacalcet 60 MG Drug: Placebo oral tablet	N/A

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 Design

Study Type:

Interventional

Actual Enrollment :

18 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Quadruple (Participant, Care Provider, 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

Study Start Date :

Jan 1, 2012

Actual Primary Completion Date :

Jun 1, 2012

Actual Study Completion Date :

Jun 1, 2014

Arms and Interventions

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	Drug: Cinacalcet 60 MG 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 oral tablet one tablet of placebo

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

Drug: Cinacalcet 60 MG

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 oral tablet

one tablet of placebo

Outcome Measures

Primary Outcome Measures

Effect of cinacalcet compared to placebo on plasma renin activity [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

Secondary Outcome Measures

effect of cinacalcet administered as single dose (compared to placebo) on plasma aldosterone and on hemodynamics [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).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 45 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Yes

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)