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

NCT02889224 | Completed

• 1 other identifier: CHUBX 2010/34
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Cushing's Syndrome

Keywords

Obesity; Cortisol; Hydrocortisone; Endocannabinoïds

Outcome Measures

Primary Outcomes (1)

• Fluctuations of 2-AG (2-arachidonoyl-Glycérol) plasma concentration in relationship to cortisol plasma concentration in obese arm compare to hypercortisolism arm.

  The primary outcome will be assessed by a measurement of plasma concentration of 2-AG during the circadian rhythm of ACTH/cortisol.

  Baseline

Secondary Outcomes (3)

• Measurement of plasma concentration of AEA (Anandamide), OEA (Oleoyl-EthanolAmide) and PEA (Palmitoyl-EthanolAmide) endocannabinoïds associated with variations of plasma cortisol in hypercortisolism arm

  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

  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.

  Baseline

Study Arms (4)

Obese

ACTIVE COMPARATOR

Subjects with BMI between 30 - 40 kg/m2 and no alteration of corticotrope axis.

Other: Obese

Hypercortisolism

EXPERIMENTAL

Subject with BMI between 18 - 40 kg/m2 and presenting a hypercortisolism defined by HAS (Haute Autorité de Santé).

Procedure: Hypercortisolism

Hydrocortisone

EXPERIMENTAL

Subject with BMI between 18 - 30 kg/m2 and with adrenal or corticotrope failure

Other: Hydrocortisone

Control

EXPERIMENTAL

Subject with BMI between 18 - 30 kg/m2 and with a pituitary or adrenal tumor without effect on corticotrope axis.

Other: Control

Interventions

Obese OTHER

Obese

Hypercortisolism PROCEDURE

Hypercortisolism

Hydrocortisone OTHER

Hydrocortisone

Control OTHER

Control

Eligibility Criteria

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

You may qualify if:

• For all patients groups:
• Age ≥ 18,
• Social security.
• " Hypercortisolism " group:
• \< 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:
• :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:

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Hospital, Bordeaux: lead

Study Sites (1)

Service d'Endocrinologie, Hopital Haut-Leveque

Pessac, 33600, France

Location

MeSH Terms

Conditions

Cushing Syndrome; Obesity

Interventions

Adiposity; Hydrocortisone

Condition Hierarchy (Ancestors)

Adrenocortical Hyperfunction; Adrenal Gland Diseases; Endocrine System Diseases; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Body Fat Distribution; Body Weights and Measures; Body Constitution; Physical Examination; Diagnostic Techniques and Procedures; Diagnosis; Body Composition; Biochemical Phenomena; Chemical Phenomena; Metabolism; Physiological Phenomena; Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids

Study Officials

• Paul PEREZ, MD

  University Hospital, Bordeaux

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 30, 2016
• First Posted: September 5, 2016
• Study Start: February 1, 2012
• Primary Completion: September 1, 2013
• Study Completion: September 1, 2013
• Last Updated: October 16, 2018

Record last verified: 2018-10

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)