Pilot Study of Aprepitant Effect on Aldosterone Secretion in Diabetic Patient (Diabetes Mellitus) With Hypertension Associated With Low Renin

NCT02811055 | Completed Phase 2

• 2 other identifiers: 2013/142/HP2015-001501-14
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

Aldosterone regulation is mediated by hormonal control, and nervous control. Autonomic nervous system action could be mediated by neuropeptides in the adrenal gland. Therefore, in pathological conditions and especially in diabetes, low-renin hypertension with normal or high plasma aldosterone could be caused by sympathetic nervous system hypertonia. Data from the literature and previous in vitro research conducted in the investigators' laboratory (INSERM U982, University of Rouen) suggest that adrenal corticosteroid secretion might be controlled by sympathetic nervous system. This neurocrine regulation of corticosteroid secretion involves locally released neuropeptides. Among them, substance P is able to stimulate aldosterone and cortisol production via NK1 receptors. A previous clinical trial conducted at the University Hospital of Rouen, APHOS (NCT00977223) studied the effects of a NK1 receptor antagonist, aprepitant, on adrenocortical secretions in healthy volunteers. The aim of the present study is to investigate the effects of a NK1 receptor antagonist, aprepitant, on adrenocortical secretions in volunteers with diabetes associated with low-renin hypertension. Aprepitant is a drug already available for the treatment of nausea induced by chemotherapy. In the present phase II trial, plasma aldosterone and cortisol levels will be measured under treatment with aprepitant versus placebo, in both basal conditions and after activation of the adrenocortical function by upright posture. All volunteers will be given the two substances (aprepitant and placebo) in a random order during two 14 day-periods separated by a 21 day-wash-out. This study should allow to determine the role of substance P in the control of corticosteroid production in human with diabetes, associated with a low-renin hypertension.

Conditions

Type 2 Diabetes; Hypertension

Outcome Measures

Primary Outcomes (1)

• Difference from baseline in Plasma aldosterone concentration

  Plasma aldosterone concentration is analyzed

  Baseline and Day 14

Secondary Outcomes (4)

• Difference from baseline in Plasma cortisol

  Baseline and Day 14

• Difference from baseline in plasma renin

  Baseline and Day 14

• Difference from baseline in blood electrolytes measurement

  Baseline and Day 14

• Difference from baseline in HOMA index

  Baseline and Day 14

Study Arms (2)

Administration of Aprepitant

EXPERIMENTAL

Administration of Aprepitant 80 mg once per day during 14 days; Blood sampling, electrocardiogram, orthostatic test and Blood Pressure Measurement are done after 14 days

Biological: Blood sampling; Procedure: Blood Pressure Measurement; Device: electrocardiogram; Procedure: orthostatic test; Drug: Administration of Aprepitant

Administration of placebo

PLACEBO COMPARATOR

Administration of Placebo once per day during 14 days; Blood sampling, electrocardiogram, orthostatic test and Blood Pressure Measurement are done after 14 days

Biological: Blood sampling; Procedure: Blood Pressure Measurement; Device: electrocardiogram; Procedure: orthostatic test; Drug: Administration of placebo

Interventions

Administration of Aprepitant DRUG

Administration of Aprepitant 80 mg once per day during 14 days

Administration of Aprepitant

Administration of placebo DRUG

Administration of placebo once per day during 14 days

Administration of placebo

Blood sampling BIOLOGICAL

Blood sampling for Plasma aldosterone, Plasma cortisol, plasma renin, plasma electrolytes after before and after administration of Aprepitant 80 mg once per day during 14 days or Administration of placebo once per day during 14 days

Administration of Aprepitant; Administration of placebo

Blood Pressure Measurement PROCEDURE

Blood Pressure Measurement before and after Administration of Aprepitant 80 mg once per day during 14 days or administration of placebo once per day during 14 days

Administration of Aprepitant; Administration of placebo

electrocardiogram DEVICE

Electrocardiogram before and after Administration of Aprepitant 80 mg once per day during 14 days or administration of placebo once per day during 14 days

Administration of Aprepitant; Administration of placebo

orthostatic test PROCEDURE

Orthostatic test after Administration of Aprepitant 80 mg once per day during 14 days or administration of placebo once per day during 14 days

Administration of Aprepitant; Administration of placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or menopausal female subjects;
• Age ranging 18-30 years old;
• Submitted to a social security regimen;
• Agreeing to the study \& Informed consent form signed;
• Body mass index (\[weight (kg)/height (m)\]²) \< 27;
• No anomaly after: complete clinical examination, pulse and blood pressure measurement, ECG;
• No biological abnormality after the following biological testing:
• Hematology: white \& red blood cells \& platelets count, haemoglobin, hematocrit, Blood biochemistry: sodium, potassium, chloride, bicarbonate, creatinine, urea, Urinary biochemistry (24 h collection): cortisol, aldosterone, Serologies: HIV, HBV, HCV,
• Subscription to national social security,
• Signed informed consent.

You may not qualify if:

• Female subject potentially pregnant,
• Subject younger than 18 year-old and older than 70 year-old,
• Subject without diabetes condition or with diabetes but normal blood pressure (below 130/80 mmHg),
• Subject with glycated hemoglobin HbA1c \< 6.5% or \>11%,
• Subject with leuconeutropenia (neutrophils below 1700/mm3),
• Subject with severe medical or surgical history,
• Patients treated with drugs metabolized by CYP3A4 and CYP2C9: corticosteroids, vitamin K , hormonal contraceptives, tolbutamide, benzodiazepines, derived from ergot, antiepileptics, hypericum, macrolides, azole antifungals.
• Patients treated with drugs interfering with the renin-angiotensin- aldosterone system : beta-blockers, diuretics , anti -aldosterone drugs , direct renin inhibitors , insulin,
• type 2 diabetes patients with a vegetative autonomic neuropathy,
• Patients with adrenal mass was diagnosed at imaging,
• hepatic or renal impairment (defined respectively by secondary clinical and biological manifestations altered hepatocyte functions or estimated glomerular filtration rate less than 60 mL / min / 1.73 m2);nephrotic syndrome (defined by hypoalbuminemia less than 30 g / L associated with proteinuria at 3 grams / 24 hours);edematous syndrome (defined by the presence of edema of the lower limbs),
• Orthostatic hypotension (defined by a decrease in systolic blood pressure of 20 mmHg and at least the diastolic blood pressure of 10 mmHg or more),
• arrhythmias or cardiac conduction,
• heart failure (NYHA class II minimum),
• epilepsy,

Sponsors & Collaborators

• University Hospital, Rouen: lead

Study Sites (1)

Rouen University Hospital

Rouen, France

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Hypertension

Interventions

Blood Specimen Collection; Electrocardiography

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Heart Function Tests; Diagnostic Techniques, Cardiovascular; Electrodiagnosis

Study Officials

• Gaétan PREVOST, MD

  University Hospital, Rouen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 25, 2016
• First Posted: June 23, 2016
• Study Start: July 13, 2017
• Primary Completion: December 5, 2020
• Study Completion: December 5, 2020
• Last Updated: March 24, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)