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

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

Interventions

BIOLOGICAL

Blood sampling

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

PROCEDURE

Blood Pressure Measurement

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

DEVICE

electrocardiogram

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

PROCEDURE

orthostatic test

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

DRUG

Administration of Aprepitant

Administration of Aprepitant 80 mg once per day during 14 days

DRUG

Administration of placebo

Administration of placebo once per day during 14 days

Sponsors & Collaborators

• University Hospital, Rouen

  lead OTHER

Principal Investigators

• Gaétan PREVOST, MD · University Hospital, Rouen

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2017-07-13

Primary Completion

2020-12-05

Completion

2020-12-05

Countries

• France

Study Locations