Social Evaluated Cold Pressor Test in Hereditary Angioedema Patients (FROSEN)

Functional Physiological, Psychological and Biochemical Reactivity to Social Evaluated Cold Pressor Test in Hereditary Angioedema Patients

This study aims to evaluate the differences in objective and subjective stress responses between patients with hereditary angioedema and healthy individuals to a stress-induced challenge like socially-evaluated cold pressure test. The study also investigates the role of psychological variables in influencing the stress response.

Study Overview

• Status: Completed
• Conditions: Hereditary Angioedema

Detailed Description

Stressful encounters, ranging from daily hassles to major life events, are ubiquitous in our everyday lives and are often responsible for significant changes in affective and cognitive processes. In various physical diseases, including hereditary angioedema (HAE) due to C1 inhibitor deficiency, stressful events are also frequently reported by patients to trigger acute attacks. These include physical stress (such as injury, pain, viral infections, medical and dental procedures, and surgery) and mental stress (including stress from life events and school or work, clinical depression, and anxiety), or stress originating from the disease itself, especially if the disease is characterized by an unpredictable nature like HEA that directly impacts patients' choices in everyday life. Available literature related to the link between HAE and stress is limited and mainly focused on the patients' narratives. Self-reported data suggested that the main HAE trigger seems to be stress, followed by physical trauma. These observations suggest analyzing the perceived psychological effects consequent to stress exposure together with biochemical and physiological responses. The effect of stress could be systematically examined in a laboratory environment using a standardized protocol that reliably induces stress and activates major stress responses in experimental contexts. A reliable test to induce stress in HAE patients combining these two aspects may be the Socially Evaluated Cold Pressor Test (SECPT). SECPT is an extension of the classical Cold Pressor Test, in which participants immerse one of their hands in ice water with socio-evaluative elements, and has been proven to be a highly efficient tool for experimental stress induction in humans. Adding social-evaluative elements to the original physical stress boosted the cortisol response, making the SECPT a well-established standard protocol in human stress research that may represent an efficient alternative to other established protocols, such as the Trier Social Stress Test, a 'gold standard' in the field. A recent review confirmed that exposure to the SECPT leads to changes in subjective feeling, and triggers a significant sharp increase in systolic and diastolic blood pressure. The present study aims to evaluate objective and subjective stress responses between HAE patients and healthy controls due to SECPT. Moreover, as secondary aims, the study wants to investigate if the presence of anxiety and depressive symptoms, as well as body appreciation, trust in the body, pain catastrophizing, pain interference, and pain intensity, affect or mediate stress response in patients and healthy subjects similarly or differently.

• Study Type: Observational
• Enrollment (Actual): 40

Contacts and Locations

Study Locations

• Italy
  • Milan, Italy, 20138
    • Istituti Clinici Scientifici Maugeri

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

The group of patients with hereditary angioedema were recruited during an out-patient visit in a tertiary care center. The group of healthy individuals were volunteers recruited from community.

Description

Inclusion Criteria:

• Documented diagnosis of hereditary angioedema due to C1 inhibitor deficiency aged between 18 and 65 years (for the group of patients)

Exclusion Criteria:

• Any type of chronic disease requiring chronic treatment (i.e. hypertension, previous myocardial infarction, diabetes, chronic heart failure, autoimmune disease, neurodegenerative disease)
• Active acute disease;
• Sars-Cov2 infection in the previous 3 months.
• An acute attack experienced within the previous week and within 72 hours after the registration (a posteriori exclusion).

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Healthy individuals; Healthy individuals with an age between 18 and 65 and matched with patients with hereditary angioedema by age and gender.
Patients with hereditary angioedema; Patients with documented diagnosis of hereditary angioedema due to C1 inhibitor deficiency and aged between 18 and 65 years.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Heart rate	Changes in the heart rate (beats per minute) from resting to SECPT condition	Baseline
Systolic arterial pressure	Changes in the systolic blood pressure (mmHg) from resting to SECPT condition	Baseline
Diastolic arterial pressure	Changes in the systolic blood pressure (mmHg) from resting to SECPT condition	Baseline
Visual Analogue Scale of perceived stress	Changes in the perceived stress due to SECP. Scores ranges from 0 (no stress) to 100 (worst stress possible)	Baseline
Concentration of inflammatory cytokines	Changes in the concentration of inflammatory cytokines (pg/ml) due to SECPT	Baseline
Concentration of plasma cathecolamines	Changes in the concentration of plasma cathecolamines (pg/ml) due to SECPT	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospital Anxiety and Depression Scale	A 14-item questionnaire subdivided in two subscales to measure anxiety and depression. Scores for each subscale ranges from 0 (absence of symptoms) to 21 (significant symptoms)	Baseline
Perceived Stress Scale (PSS-10)	A 10-item questionnaire to measure stress levels related to the perception of unpredicable, uncontrollable, and overloading nature of life. Scores ranges from 0 (low levels) to 40 (high levels).	Baseline
Multidimensional Assessment of Interoceptive Awareness Version 1	A 32-item questionnaire to measure Interoceptive Awareness. Scores ranges from 0 (low interoceptive awareness) to 160 (high interoceptive awareness).	Baseline
Body Appreciation Scale-2 (BAS-2)	A 10-item questionnaire to measure appreciation. Scores ranges from 10 (low body appreciation) to 50 (high body appreciation).	Baseline
Functionality Appreciation Scale (FAS)	A 7-item questionnaire to measure body appreciation. Scores ranges from 0 (low functionality appreciation) to 35 (high functionality appreciation)	Baseline
Pain Catastrophizing Scale (PCS)	A 13-item questionnaire to measure pain-related catastrophizing. Scores ranges from 0 (low catastrophizing ) to 52 (high catastrophizing).	Baseline

Collaborators and Investigators

• Sponsor: Istituti Clinici Scientifici Maugeri SpA

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2023
• Primary Completion (Actual): March 18, 2024
• Study Completion (Actual): March 18, 2024

Study Registration Dates

• First Submitted: May 7, 2024
• First Submitted That Met QC Criteria: May 13, 2024
• First Posted (Actual): May 16, 2024

Study Record Updates

• Last Update Posted (Actual): May 16, 2024
• Last Update Submitted That Met QC Criteria: May 13, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Stress; Autonomic nervous system; Hereditary Angioedema; Rare disease; Body appreciation; Cold pressor test
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Vascular; Hypersensitivity; Urticaria; Hereditary Complement Deficiency Diseases; Primary Immunodeficiency Diseases; Angioedema; Angioedemas, Hereditary
• Other Study ID Numbers: 2774CE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No