Clinical trial NCT05162950: Effects and Importance of Epinephrine/Adrenalin Deficiency in CAH
Official title: Effects and Importance of Epinephrine/Adrenalin Deficiency in CAH
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Congenital Adrenal Hyperplasia
Lead sponsor: Region Stockholm
Sponsor class: OTHER_GOV
First posted: 2021-12-20
Enrollment: 120
Sex: ALL
Minimum age (years): 16
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Men and women with congenital adrenal hyperplasia due to 21-hydroxylase deficienc. Sex and age matched controls.

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.

Eligibility criteria: Inclusion Criteria:

* CAH due to 21-hydroxylase deficiency,

Exclusion Criteria:

* Cardiovascular disease

Primary outcomes:
measure: epinephrine level
timeFrame: 2022 December 31
Secondary outcomes:
measure: Hospital Anxiety Depression Scale
timeFrame: 2022 December 31
measure: Mental Fatigue scale
timeFrame: 2022 December 31
measure: Liebowitz anxiety scale
timeFrame: 2022 December 31
measure: Karolinska Exhaustion disorder scale
timeFrame: 2022 December 31
measure: sleep questionnaire
timeFrame: 2022 December 31
Other outcomes:
measure: Orthostatic blood pressure
timeFrame: 2022 December 31
measure: CYP21A2 genotype
timeFrame: 2022 December 31
Locations:
city: Stockholm
country: Sweden
facility: Karolinska University hospital
state: (State)
Study officials:
affiliation: Karolinska University Hospital
name: Fredrika Gauffin, MDPhD
role: STUDY_DIRECTOR
References: