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

Primary Purpose

Cushing's Syndrome

Status

Completed

Phase

Not Applicable

Locations

France

Study Type

Interventional

Intervention

Obese

Hypercortisolism

Hydrocortisone

Control

About this trial

This is an interventional other trial for Cushing's Syndrome focused on measuring Obesity, Cortisol, Hydrocortisone, Endocannabinoïds

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Service d'Endocrinologie, Hopital Haut-Leveque

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Experimental

Arm Label

Obese

Hypercortisolism

Hydrocortisone

Control

Arm Description

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

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

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

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

The secondary outcome wille be assessed by a measurement of plasma concentration of AEA, OEA and PEA during the circadian rhythm of ACTH/cortisol.

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

Measurement of plasma concentration of AEA (Anandamide), OEA (Oleoyl-EthanolAmide) and PEA (Palmitoyl-EthanolAmide) endocannabinoïds in control arm who have no cortisol production problem.

Measurement of plasma concentration of AEA, OEA and PEA during the circadian rhythm of ACTH/cortisol

Full Information

NCT ID

NCT02889224

First Posted

August 30, 2016

Last Updated

October 11, 2018

Sponsor

University Hospital, Bordeaux

1. Study Identification

Unique Protocol Identification Number

NCT02889224

Brief Title

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

Acronym

VISECA

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2018

Overall Recruitment Status

Completed

Study Start Date

February 2012 (undefined)

Primary Completion Date

September 2013 (Actual)

Study Completion Date

September 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University Hospital, Bordeaux

4. Oversight

Data Monitoring Committee

5. Study Description

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

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cushing's Syndrome

Keywords

Obesity, Cortisol, Hydrocortisone, Endocannabinoïds

7. Study Design

Primary Purpose

Other

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

40 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Obese

Arm Type

Active Comparator

Arm Description

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

Arm Title

Hypercortisolism

Arm Type

Experimental

Arm Description

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

Arm Title

Hydrocortisone

Arm Type

Experimental

Arm Description

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

Arm Title

Control

Arm Type

Experimental

Arm Description

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

Intervention Type

Other

Intervention Name(s)

Obese

Intervention Type

Procedure

Intervention Name(s)

Hypercortisolism

Intervention Type

Other

Intervention Name(s)

Hydrocortisone

Intervention Type

Other

Intervention Name(s)

Control

Primary Outcome Measure Information:

Title

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

Description

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

Time Frame

Baseline

Secondary Outcome Measure Information:

Title

Description

The secondary outcome wille be assessed by a measurement of plasma concentration of AEA, OEA and PEA during the circadian rhythm of ACTH/cortisol.

Time Frame

Baseline and day 6

Title

Description

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

Time Frame

Baseline

Title

Measurement of plasma concentration of AEA (Anandamide), OEA (Oleoyl-EthanolAmide) and PEA (Palmitoyl-EthanolAmide) endocannabinoïds in control arm who have no cortisol production problem.

Description

Measurement of plasma concentration of AEA, OEA and PEA during the circadian rhythm of ACTH/cortisol

Time Frame

Baseline

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Paul PEREZ, MD

Organizational Affiliation

University Hospital, Bordeaux

Official's Role

Study Chair

Facility Information:

Facility Name

Service d'Endocrinologie, Hopital Haut-Leveque

City

Pessac

ZIP/Postal Code

33600

Country

France

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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