## Protocol Section
### Identification Module
**NCT ID:** NCT06414252

**Acronym:** FROSEN

**Brief Title:** Social Evaluated Cold Pressor Test in Hereditary Angioedema Patients

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

#### Organization Study ID Info
**ID:** 2774CE
#### Organization
**Class:** OTHER
**Full Name:** Istituti Clinici Scientifici Maugeri SpA
### Status Module
#### Completion Date
**Date:** 2024-03-18

**Type:** ACTUAL

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-16

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-13

**Overall Status:** COMPLETED

#### Primary Completion Date
**Date:** 2024-03-18

**Type:** ACTUAL

#### Start Date
**Date:** 2023-05-15

**Type:** ACTUAL

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-16
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-07
**Study First Submit QC Date:** 2024-05-13
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Istituti Clinici Scientifici Maugeri SpA

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** 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.

**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.

### Conditions Module

**Conditions:**

- Hereditary Angioedema

**Keywords:**

- Hereditary Angioedema

- Autonomic nervous system

- Cold pressor test

- Stress

- Body appreciation

- Rare disease

### Design Module

#### Design Info

**Observational Model:** CASE_CONTROL

**Time Perspective:** CROSS_SECTIONAL

#### Enrollment Info

**Count:** 40

**Type:** ACTUAL

**Study Type:** OBSERVATIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Patients with documented diagnosis of hereditary angioedema due to C1 inhibitor deficiency and aged between 18 and 65 years.

**Label:** Patients with hereditary angioedema

#### Arm Group 2

**Description:** Healthy individuals with an age between 18 and 65 and matched with patients with hereditary angioedema by age and gender.

**Label:** Healthy individuals

### Outcomes Module

#### Primary Outcomes

**Description:** Changes in the heart rate (beats per minute) from resting to SECPT condition

**Measure:** Heart rate

**Time Frame:** Baseline

**Description:** Changes in the systolic blood pressure (mmHg) from resting to SECPT condition

**Measure:** Systolic arterial pressure

**Time Frame:** Baseline

**Description:** Changes in the systolic blood pressure (mmHg) from resting to SECPT condition

**Measure:** Diastolic arterial pressure

**Time Frame:** Baseline

**Description:** Changes in the perceived stress due to SECP. Scores ranges from 0 (no stress) to 100 (worst stress possible)

**Measure:** Visual Analogue Scale of perceived stress

**Time Frame:** Baseline

**Description:** Changes in the concentration of inflammatory cytokines (pg/ml) due to SECPT

**Measure:** Concentration of inflammatory cytokines

**Time Frame:** Baseline

**Description:** Changes in the concentration of plasma cathecolamines (pg/ml) due to SECPT

**Measure:** Concentration of plasma cathecolamines

**Time Frame:** Baseline

#### Secondary Outcomes

**Description:** 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)

**Measure:** Hospital Anxiety and Depression Scale

**Time Frame:** Baseline

**Description:** 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).

**Measure:** Perceived Stress Scale (PSS-10)

**Time Frame:** Baseline

**Description:** A 32-item questionnaire to measure Interoceptive Awareness. Scores ranges from 0 (low interoceptive awareness) to 160 (high interoceptive awareness).

**Measure:** Multidimensional Assessment of Interoceptive Awareness Version 1

**Time Frame:** Baseline

**Description:** A 10-item questionnaire to measure appreciation. Scores ranges from 10 (low body appreciation) to 50 (high body appreciation).

**Measure:** Body Appreciation Scale-2 (BAS-2)

**Time Frame:** Baseline

**Description:** A 7-item questionnaire to measure body appreciation. Scores ranges from 0 (low functionality appreciation) to 35 (high functionality appreciation)

**Measure:** Functionality Appreciation Scale (FAS)

**Time Frame:** Baseline

**Description:** A 13-item questionnaire to measure pain-related catastrophizing. Scores ranges from 0 (low catastrophizing ) to 52 (high catastrophizing).

**Measure:** Pain Catastrophizing Scale (PCS)

**Time Frame:** Baseline

### Eligibility Module

**Eligibility Criteria:** 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).

**Maximum Age:** 65 Years

**Minimum Age:** 18 Years

**Sampling Method:** NON_PROBABILITY_SAMPLE

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

**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.

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Milan

**Country:** Italy

**Facility:** Istituti Clinici Scientifici Maugeri

**Zip:** 20138

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000014652

- Term: Vascular Diseases

- ID: D000002318

- Term: Cardiovascular Diseases

- ID: D000014581

- Term: Urticaria

- ID: D000017445

- Term: Skin Diseases, Vascular

- ID: D000012871

- Term: Skin Diseases

- ID: D000006969

- Term: Hypersensitivity, Immediate

- ID: D000006967

- Term: Hypersensitivity

- ID: D000007154

- Term: Immune System Diseases

- ID: D000081208

- Term: Hereditary Complement Deficiency Diseases

- ID: D000081207

- Term: Primary Immunodeficiency Diseases

- ID: D000030342

- Term: Genetic Diseases, Inborn

- ID: D000007153

- Term: Immunologic Deficiency Syndromes

### Condition Browse Module - Browse Branches

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

- Abbrev: BC01

- Name: Infections

- Abbrev: BC08

- Name: Respiratory Tract (Lung and Bronchial) Diseases

- Abbrev: BC14

- Name: Heart and Blood Diseases

- Abbrev: BC17

- Name: Skin and Connective Tissue Diseases

- Abbrev: BC20

- Name: Immune System Diseases

- Abbrev: BC16

- Name: Diseases and Abnormalities at or Before Birth

- Abbrev: BC18

- Name: Nutritional and Metabolic Diseases

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M24518

- Name: Rare Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M14978

- Name: Respiratory Tract Infections

- Relevance: LOW

- As Found: Unknown

- ID: M4127

- Name: Angioedema

- Relevance: HIGH

- As Found: Angioedema

- ID: M27584

- Name: Angioedemas, Hereditary

- Relevance: HIGH

- As Found: Hereditary Angioedema

- ID: M17400

- Name: Vascular Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M17330

- Name: Urticaria

- Relevance: LOW

- As Found: Unknown

- ID: M15674

- Name: Skin Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M19714

- Name: Skin Diseases, Vascular

- Relevance: LOW

- As Found: Unknown

- ID: M10018

- Name: Hypersensitivity

- Relevance: LOW

- As Found: Unknown

- ID: M10020

- Name: Hypersensitivity, Immediate

- Relevance: LOW

- As Found: Unknown

- ID: M10200

- Name: Immune System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M6879

- Name: Deficiency Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M2286

- Name: Hereditary Complement Deficiency Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M10199

- Name: Immunologic Deficiency Syndromes

- Relevance: LOW

- As Found: Unknown

- ID: M2285

- Name: Primary Immunodeficiency Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M23686

- Name: Genetic Diseases, Inborn

- Relevance: LOW

- As Found: Unknown

- ID: M16355

- Name: Syndrome

- Relevance: LOW

- As Found: Unknown

- ID: T2734

- Name: Hereditary Angioedema

- Relevance: HIGH

- As Found: Hereditary Angioedema

### Condition Browse Module - Meshes

- ID: D000000799

- Term: Angioedema

- ID: D000054179

- Term: Angioedemas, Hereditary

### Intervention Browse Module - Browse Branches

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M26365

- Name: Complement C1 Inhibitor Protein

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-31
