In Vivo Study of Interactions Between the Endocannabinoid System and the Corticotropic Axis in Man (VISECA)

October 11, 2018 updated by: University Hospital, Bordeaux

Working hypothesis: the interactions between the endogenous endocannabinoïds (ECS) - and cortisol, the end product of the Hypothalamo-Pituitary-Adrenal (HPA) axis may play a role in the pathophysiology of Cushing's syndrome.

The investigators speculate that:

  • acute or chronic variations in plasma cortisol may induce changes in the activity of the ECS
  • that there is a circadian rhythm of the ECS driven by the rythm of plasma cortisol

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The study aim to identify the relationship between the ECS and the HPA axis in humans with a main objective to assess if Cushing's syndrome induces changes in the ECS activity.

For this purpose:

  1. the investigors will compare plasma levels of ECS between obese controls and patients with Cushing's syndrome
  2. the investigors will compare plasma levels of ECS in patients with Cushing's syndrome before and immediately after curative surgery
  3. the investigors will compare plasma levels of ECS in patients with hypoadrenalism before and after the intake of substitutive doses of hydrocortisone
  4. the investigors will evaluate the plasma levels of ECS during a short synacthen test in healthy subjects.

Study Type

Interventional

Enrollment (Actual)

40

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

  • France
      • Pessac, France, 33600
        • Service d'Endocrinologie, Hopital Haut-Leveque

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

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

For all patients groups:

  • Age ≥ 18,
  • Social security.

" Hypercortisolism " group:

  • 18 < BMI < 40 kg/m2,
  • Cushing's syndrome in front of :
  • impaired 1 mg dexamethasone test (08:00 A.M. cortisol > 50 nmol/L)
  • qualitative and quantitative disrupted circadian rhythm of cortisol with increased plasma concentrations
  • free urinary cortisol upper normal range (90 µg/24H),
  • Hypercortisolism that can be treated with surgery (adrenal adenoma treated with adrenalectomy or Cushing disease treated with pituitary surgery).

" Obese " group:

  • Obese patients: 30 < BMI < 40 kg/m2,
  • Normal HPA axis function:
  • 08:00 A.M. cortisol > 250 nmol/L and peak above 550 nmol/L after 1 mg SST,
  • Normal 24H free urinary cortisol and dexamethasone test. " Control " group:
  • Lean or overweight patients (18 < BMI < 30 kg/m2),
  • Non cortisol secreting pituitary or adrenal tumor,
  • Patient in whom a biological evaluation of the HPA axis is recommended.

" Hydrocortisone " group:

  • Lean or overweight patients (18 < BMI < 30 kg/m2),
  • Primary or secondary adrenal insufficiency,
  • With a need for hydrocortisone supplementation.

Exclusion Criteria:

  • Patients with eating disorders, major depressive disorders or psychiatric disorders other than Cushing's syndrome,
  • Cannabis consumption, alcoholism or drug addiction,
  • Active smoking,
  • cortisone treatment other than hydrocortisone,
  • Pregnancy or feeding,
  • Surgery for obesity,
  • Incapability,
  • Pathology that is life-threatening in the short term,
  • Any situation that interfere with study or is risked for patient.

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: Other
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Obese
Subjects with BMI between 30 - 40 kg/m2 and no alteration of corticotrope axis.
Other: Obese
Experimental: Hypercortisolism
Subject with BMI between 18 - 40 kg/m2 and presenting a hypercortisolism defined by HAS (Haute Autorité de Santé).
Procedure: Hypercortisolism
Experimental: Hydrocortisone
Subject with BMI between 18 - 30 kg/m2 and with adrenal or corticotrope failure
Other: Hydrocortisone
Experimental: Control
Subject with BMI between 18 - 30 kg/m2 and with a pituitary or adrenal tumor without effect on corticotrope axis.
Other: Control

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Fluctuations of 2-AG (2-arachidonoyl-Glycérol) plasma concentration in relationship to cortisol plasma concentration in obese arm compare to hypercortisolism arm.
Time Frame: Baseline
The primary outcome will be assessed by a measurement of plasma concentration of 2-AG during the circadian rhythm of ACTH/cortisol.
Baseline

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Measurement of plasma concentration of AEA (Anandamide), OEA (Oleoyl-EthanolAmide) and PEA (Palmitoyl-EthanolAmide) endocannabinoïds associated with variations of plasma cortisol in hypercortisolism arm
Time Frame: Baseline and day 6
The secondary outcome wille be assessed by a measurement of plasma concentration of AEA, OEA and PEA during the circadian rhythm of ACTH/cortisol.
Baseline and day 6
Measurement of plasma concentration of AEA (Anandamide), OEA (Oleoyl-EthanolAmide) and PEA (Palmitoyl-EthanolAmide) endocannabinoïds associated with variations of plasma cortisol in hydrocortisone arm
Time Frame: Baseline
Measurement of plasma concentration of AEA, OEA and PEA on 07:30 A.M. ± 1 hour (fasting), 08:00 A.M. ± 1 hour (fasting), 09:00 A.M. ± 1 hour, 10:00 A.M. ± 1 hour, 04:00 P.M. ± 1 hour
Baseline
Measurement of plasma concentration of AEA (Anandamide), OEA (Oleoyl-EthanolAmide) and PEA (Palmitoyl-EthanolAmide) endocannabinoïds in control arm who have no cortisol production problem.
Time Frame: Baseline
Measurement of plasma concentration of AEA, OEA and PEA during the circadian rhythm of ACTH/cortisol
Baseline

Collaborators and Investigators

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

Sponsor

University Hospital, Bordeaux

Investigators

  • Study Chair: Paul PEREZ, MD, University Hospital, Bordeaux

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

February 1, 2012

Primary Completion (Actual)

September 1, 2013

Study Completion (Actual)

September 1, 2013

Study Registration Dates

First Submitted

August 30, 2016

First Submitted That Met QC Criteria

August 30, 2016

First Posted (Estimate)

September 5, 2016

Study Record Updates

Last Update Posted (Actual)

October 16, 2018

Last Update Submitted That Met QC Criteria

October 11, 2018

Last Verified

October 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CHUBX 2010/34

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

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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