Effects and Importance of Epinephrine/Adrenalin Deficiency in CAH

Congenital Adrenal Hyperplasia Clinical Trial

Official title:

Effects and Importance of Epinephrine/Adrenalin Deficiency in CAH

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT05162950
• Other study ID #: CAH and epinephrine
• Status: Enrolling by invitation
• Start date: September 1, 2020
• Est. completion date: December 31, 2022

Study information

• Verified date: December 2021
• Source: Region Stockholm
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 120
• Est. completion date: December 31, 2022
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 16 Years to 65 Years

Eligibility

Inclusion Criteria:

• CAH due to 21-hydroxylase deficiency,

Exclusion Criteria:

• Cardiovascular disease

Related Conditions & MeSH terms

• Adrenal Hyperplasia, Congenital
• Adrenogenital Syndrome
• Congenital Adrenal Hyperplasia
• Hyperplasia

Intervention

Diagnostic Test:
• physical exercise as a standardized high intensity exercise test
High intensity exercise test, cycling, performed at the Karolinska University Hospital

Behavioral:
• 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

Locations

Country	Name	City	State
Sweden	Karolinska University hospital	Stockholm	(State)

Sponsors (1)

Lead Sponsor	Collaborator
Region Stockholm

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Orthostatic blood pressure	Blood pressure measured lying down and standing for 10 minutes	2022 December 31
Other	CYP21A2 genotype	mutation analysis	2022 December 31
Primary	epinephrine level	Measured methoxy-catecholamine at maximum exercise test, cycling test.	2022 December 31
Secondary	Hospital Anxiety Depression Scale	stress vulnerability	2022 December 31
Secondary	Mental Fatigue scale	stress vulnerability	2022 December 31
Secondary	Liebowitz anxiety scale	stress vulnerability	2022 December 31
Secondary	Karolinska Exhaustion disorder scale	stress vulnerability	2022 December 31
Secondary	sleep questionnaire	stress vulnerability	2022 December 31