Effects and Importance of Epinephrine/Adrenalin Deficiency in CAH

NCT ID: NCT05162950

Last Updated: 2022-01-11

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 120 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2020-09-01
• Study Completion Date: 2022-12-31

Brief Summary

Individuals with CAH produce lower levels of epinephrine (adrenalin) than controls. This can be correlated to the CYP21A2 genotype and is most pronounced in the classic forms. Individuals with CAH have an increased risk of developing hypoglycemia because both cortisol and epinephrine are important counter regulatory hormones. Stress dosing is essential in situations of increased physical stress such as infections with fever for example.

Glucocorticoid treatment and stress dosing cannot compensate fully during physical stress neither for the reaction to psychological stress. This may render various types of difficulties in the individual's life.

We aim to investigate if the deficient epinephrine production can be confirmed and if it is related to the increased level of anxiety and vulnerability to stress that we observe in the patients.

Specific aims of the study:

• Analyse the epinephrine/adrenalin production in patients with CAH using measurements of epinephrine and metanephrine in blood, during an exercise test
• Assess stress vulnerability and anxiety using validated questionnaires
• Correlate the results to severity of disease, CYP21A2 genotype
• Investigate if psychological and somatic stress symptoms are related to the epinephrine production capacity.

Detailed Description

After written informed consent study subjects, patients and controls, are invited to fill in a web based survey with the validated questionnaires. A link to the survey, expected to take 30 - 60 minutes to complete, is mailed to to the subjects . A subgroup of study subjects are invited to perform an ergo-spirometri test followed by the exercise test at the hospital. They are asked not to eat for 6 hours or drink any coffe during the day before the test. A venous catheter is used for blood sampling during the exercise. ECG, an orthostatic blood pressure test and a the ergo-spirometry test are performed before the subject is asked to do the exercise test, a cycling maximum test. Blood glucose, lactate, are followed every 4 minutes. Adrenal androgens, cortisol, insulin and methoxy-catecholamine are measured before and when the subject has reached maximum effort load and the test is ended.

The physical capacity, orthostatic blood pressure and the blood test results are related to the severity of CAH and to the maximum level of methoxy-cathecholamine produced by each individual. In the larger group of individuals, not taking part in the exercise test but completing the survey the genotype is correlated to the questionnaire results.

Conditions

Congenital Adrenal Hyperplasia

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

SW CAH

Patients with 21-hydroxylase deficiency, salt wasting form.

physical exercise as a standardized high intensity exercise test

Intervention Type: DIAGNOSTIC_TEST

High intensity exercise test, cycling, performed at the Karolinska University Hospital

Stress vulnerability

Intervention Type: BEHAVIORAL

Web based survey of validated psychological questionnaires measuring fatigue (MFS), exhaustion disorder (KEDS), anxiety (LSAS-SR, HADS), depression (HADS), and Karolinska sleep questionnaire

SV CAH

Patients with 21-hydroxylase deficiency, simple virilising form.

physical exercise as a standardized high intensity exercise test

Intervention Type: DIAGNOSTIC_TEST

High intensity exercise test, cycling, performed at the Karolinska University Hospital

Stress vulnerability

Intervention Type: BEHAVIORAL

Web based survey of validated psychological questionnaires measuring fatigue (MFS), exhaustion disorder (KEDS), anxiety (LSAS-SR, HADS), depression (HADS), and Karolinska sleep questionnaire

NC CAH

Patients with 21-hydroxylase deficiency, non-classic form.

physical exercise as a standardized high intensity exercise test

Intervention Type: DIAGNOSTIC_TEST

High intensity exercise test, cycling, performed at the Karolinska University Hospital

Stress vulnerability

Intervention Type: BEHAVIORAL

Web based survey of validated psychological questionnaires measuring fatigue (MFS), exhaustion disorder (KEDS), anxiety (LSAS-SR, HADS), depression (HADS), and Karolinska sleep questionnaire

Carrier CAH

Healthy individuals, heterozygous carriers a mutation in the CYP21A2 gene. Recruited among parents of patients with CAH.

physical exercise as a standardized high intensity exercise test

Intervention Type: DIAGNOSTIC_TEST

High intensity exercise test, cycling, performed at the Karolinska University Hospital

Stress vulnerability

Intervention Type: BEHAVIORAL

Web based survey of validated psychological questionnaires measuring fatigue (MFS), exhaustion disorder (KEDS), anxiety (LSAS-SR, HADS), depression (HADS), and Karolinska sleep questionnaire

Control

Healthy sex and age matched controls

physical exercise as a standardized high intensity exercise test

Intervention Type: DIAGNOSTIC_TEST

High intensity exercise test, cycling, performed at the Karolinska University Hospital

Stress vulnerability

Intervention Type: BEHAVIORAL

Web based survey of validated psychological questionnaires measuring fatigue (MFS), exhaustion disorder (KEDS), anxiety (LSAS-SR, HADS), depression (HADS), and Karolinska sleep questionnaire

Interventions

physical exercise as a standardized high intensity exercise test

High intensity exercise test, cycling, performed at the Karolinska University Hospital

Intervention Type: DIAGNOSTIC_TEST

Stress vulnerability

Web based survey of validated psychological questionnaires measuring fatigue (MFS), exhaustion disorder (KEDS), anxiety (LSAS-SR, HADS), depression (HADS), and Karolinska sleep questionnaire

Intervention Type: BEHAVIORAL

Other Intervention Names

Validated questionnaires

Eligibility Criteria

Inclusion Criteria

• CAH due to 21-hydroxylase deficiency,

Exclusion Criteria

• Cardiovascular disease

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Region Stockholm

OTHER_GOV

Sponsor Role: lead

Responsible Party

Anna Jung Nordenstrom

Adj Professor, Senior Consultant

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Fredrika Gauffin, MDPhD

Role: STUDY_DIRECTOR

Karolinska University Hospital

Locations

Karolinska University hospital

Stockholm, (State), Sweden

Countries

Sweden

Other Identifiers

CAH and epinephrine

Identifier Type: -

Identifier Source: org_study_id