Assessment of Persistent Cognitive Impairment After Cure of Cushing's Disease (MEMOCUSH)

Cognitive Sequels of Cushing Syndrome

Cushing's disease is a state of chronic endogenous glucocorticoid excess. Cushing's disease is responsible for increased morbidity and mortality. Recent studies have pinpointed the frequency of somatic sequelas and persistent alteration in quality of life despite the cure of the disease. More specifically, a few studies have described persistent psychopathology, maladaptive personality and cognitive impairments in patients with a history of Cushing's disease. Among these, hippocampal memory deficits have been found in the majority of studies, a finding that is consistent with the alterations described in hippocampal neurons during chronic exposure to glucocorticoids. However, the tools currently available to assess hippocampal-dependent memory are multiple, sometimes difficult to perform by clinicians and to analyze or may lack of diagnostic sensitivity. The investigators have recently developed an original tool, the virtual radial task in 3D, which has shown to be reliable to detect subtle alterations in hippocampal-dependent memory in several human diseases. The primary aim of the study is the evaluation of persistent cognitive impairments (hippocampal memory) in patients cured of Cushing's disease for at least one year using the virtual radial task in 3D and to compare it with that obtained with classical cognitive tests.

Study Overview

• Status: Unknown
• Conditions: Cushing's Disease
• Intervention / Treatment: Device: Virtual radial task in 3D

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Antoine Tabarin, Pr; Email: antoine.tabarin@chu-bordeaux.fr

Study Locations

• France
  • Pessac, France, 33604
    • Hopital Du Haut-Leveque
    • Contact: Antoine Tabarin, Pr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Patients :

• history of Cushing's Disease
• aged : 18 - 60 years
• Biological remission of Cushing's disease for at least one year
• Affiliation to Social Security
• Informed consent signed by patient and investigator (at the latest the inclusion's day, before study's exams)

For controls :

• People aged 18 to 60 years matched to patients for age, sex and educational level
• Affiliation to Social Security
• Informed consent signed by patient and investigator (at the latest the inclusion's day, before study's exams)

Exclusion Criteria:

For patients :

• Persistent hypercortisolism (even mild)
• Current treatment of hypercortisolism with drugs
• Obesity (BMI >30 kg/m²)
• Alcohol or drug addiction present or past
• Growth hormone deficit
• Diabetes mellitus with hemoglobin A1c > 7.5% and/or fasting blood glucose > 1.4 g/L
• History of pituitary radiotherapy
• History of cerebrovascular or neuro-cerebral disease
• untreated dysthyroidism
• Current psychotropic drug treatment
• Pregnancy
• Use of glucocorticoids in the last 3 months before study (aside hydrocortisone replacement therapy)
• Excessive hydrocortisone replacement therapy (unadjusted to weight and/or with evening administration)

For controls :

• Obesity (BMI >30 kg/m²)
• Alcohol or drug addiction present or past
• Current psychotropic drug treatment
• History of cerebrovascular or neuro-cerebral disease
• Current pregnancy
• Chronical use of corticoid (> 1 month), current or past
• Use of glucocorticoids in the last 3 months before study (aside hydrocortisone replacement therapy)
• Diabetes mellitus with hemoglobin A1c > 7.5% and/or fasting blood glucose > 1.4 g/L
• Obesity (BMI >30 kg/m²)
• untreated dysthyroidism

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients; Virtual radial task in 3D	Device: Virtual radial task in 3D; The virtual radial task is a labyrinth in 3D with twelve ways. The primary aim of our study is the evaluation of persistent cognitive impairments (hippocampal memory) according to the responses of participants after instructions to choose the right way in the labyrinth.
Experimental: Controls; Virtual radial task in 3D	Device: Virtual radial task in 3D; The virtual radial task is a labyrinth in 3D with twelve ways. The primary aim of our study is the evaluation of persistent cognitive impairments (hippocampal memory) according to the responses of participants after instructions to choose the right way in the labyrinth.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of right answers at virtual radial task in 3D	Comparison of right answers in patients cured of Cushing's disease and in controls.	baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
General Quality of life	Comparison of quality of life of patients and controls with validated general questionnaire : SF-36 (SF for Short Form health survey)	baseline
Specific Quality of life for Cushing's Disease	Comparison of quality of life of patients and controls with validated specific questionnaire for Cushing's Disease : Cushing-QoL	baseline
Number of participants with anxiety	Evaluation of anxiety in the two groups with Hospital Anxiety and Depression Scale (HADS) scale (questionnaire)	baseline
Number of participants with depression with MADRS	Evaluation of depression in the two groups with Montgomery and Asberg Depression Rating Scale (MADRS) (questionnaire)	baseline
Number of participants with depression with HADS	Evaluation of depression in the two groups with Hospital Anxiety and Depression Scale (HADS) scale (questionnaire)	baseline
Intensity of Cushing's syndrome	Intensity of Cushing's disease will be evaluated with mean of free urinary cortisol. Hypothesis : intensity of hypercortisolism is correlated with sequels after cure.	baseline

Collaborators and Investigators

• Sponsor: Institut National de la Santé Et de la Recherche Médicale, France
• Investigators: Principal Investigator: Antoine Tabarin, Pr, Hôpital Haut Lévêque - Pessac (France)

Publications and helpful links

General Publications

• Pupier E, Santos A, Etchamendy N, Lavielle A, Ferriere A, Marighetto A, Resmini E, Cota D, Webb SM, Tabarin A. Impaired quality of life, but not cognition, is linked to a history of chronic hypercortisolism in patients with Cushing's disease in remission. Front Endocrinol (Lausanne). 2022 Aug 8;13:934347. doi: 10.3389/fendo.2022.934347. eCollection 2022.

Study record dates

Study Major Dates

• Study Start: November 1, 2015
• Primary Completion (Anticipated): May 1, 2016
• Study Completion (Anticipated): May 1, 2017

Study Registration Dates

• First Submitted: November 3, 2015
• First Submitted That Met QC Criteria: November 10, 2015
• First Posted (Estimate): November 13, 2015

Study Record Updates

• Last Update Posted (Estimate): November 13, 2015
• Last Update Submitted That Met QC Criteria: November 10, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Endocrine Gland Neoplasms; Hypothalamic Diseases; Hyperpituitarism; Pituitary Diseases; Adenoma; Pituitary Neoplasms; ACTH-Secreting Pituitary Adenoma; Pituitary ACTH Hypersecretion
• Other Study ID Numbers: C15-02; IDRCB (Registry Identifier: 2022-A02601-42)