Hereditary AngioedemaFROSENNCT06414252
Social Evaluated Cold Pressor Test in Hereditary Angioedema Patients
An observational study of Hereditary Angioedema, run by Istituti Clinici Scientifici Maugeri SpA at 1 site in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Hereditary Angioedema
- How many people
- 40 participants
- Where
- 1 siteItaly
- Study dates
- 15 May 2023to 18 Mar 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- 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.
Who may be able to join
- Documented diagnosis of hereditary angioedema due to C1 inhibitor deficiency aged between 18 and 65 years (for the group of patients)
Who cannot join
- 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).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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
- Hereditary Angioedema
- Keywords
- Hereditary Angioedema, Autonomic nervous system, Cold pressor test, Stress, Body appreciation, Rare disease
- Medical subject headings
- Angioedemas, Hereditary, Rare Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Patients with hereditary angioedema | Patients with documented diagnosis of hereditary angioedema due to C1 inhibitor deficiency and aged between 18 and 65 years. | |
| Healthy individuals | Healthy individuals with an age between 18 and 65 and matched with patients with hereditary angioedema by age and gender. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Heart rate
Changes in the heart rate (beats per minute) from resting to SECPT condition
Measured: Baseline
Systolic arterial pressure
Changes in the systolic blood pressure (mmHg) from resting to SECPT condition
Measured: Baseline
Diastolic arterial pressure
Changes in the systolic blood pressure (mmHg) from resting to SECPT condition
Measured: 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)
Measured: Baseline
Concentration of inflammatory cytokines
Changes in the concentration of inflammatory cytokines (pg/ml) due to SECPT
Measured: Baseline
Concentration of plasma cathecolamines
Changes in the concentration of plasma cathecolamines (pg/ml) due to SECPT
Measured: Baseline
Secondary outcomes (6)
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)
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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)
Measured: Baseline
Pain Catastrophizing Scale (PCS)
A 13-item questionnaire to measure pain-related catastrophizing. Scores ranges from 0 (low catastrophizing ) to 52 (high catastrophizing).
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2024
- Study start15 May 2023
- Primary completion18 Mar 2024
- Study completion18 Mar 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hereditary AngioedemaStudies of the same condition, open and under way.
- More trials run by Istituti Clinici Scientifici Maugeri SpAThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Istituti Clinici Scientifici Maugeri SpA
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06414252
- Sponsor's protocol ID
- 2774CE
- Acronym
- FROSEN
- Status last verified
- May 2024
- First submitted
- 7 May 2024
- Last updated
- 16 May 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
De Maria B, Ranucci L, Gino C, Cesoni Marcelli A, Zingale LC, Zulueta A, Dalla Vecchia LA, Gorini A, Perego F. Functional physiological, psychological, and biochemical reactivity to socially evaluated cold pressor test in hereditary angioedema patients (FRoSEn). Front Immunol. 2026 Jan 7;16:1736589. doi: 10.3389/fimmu.2025.1736589. eCollection 2025.
PubMed 41573571
Study at a glance
From the registry record, last updated by the sponsor on 16 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Functional Physiological, Psychological and Biochemical Reactivity to Social Evaluated Cold Pressor Test in Hereditary Angioedema Patients
- ClinicalTrials.gov ID
- NCT06414252
- Acronym / sponsor ID
- FROSEN / 2774CE
- Conditions
- Hereditary Angioedema
- Keywords
- Hereditary Angioedema, Autonomic nervous system, Cold pressor test, Stress, Body appreciation, Rare disease
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Istituti Clinici Scientifici Maugeri SpAUniversity, hospital or other
- Study start
- 15 May 2023 (actual)
- Primary completion
- 18 Mar 2024 (actual)
- Study completion
- 18 Mar 2024 (actual)
- First posted
- 16 May 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Patients with hereditary angioedema | – | –Patients with documented diagnosis of hereditary angioedema due to C1 inhibitor deficiency and aged between 18 and 65 years. |
| Healthy individuals | – | –Healthy individuals with an age between 18 and 65 and matched with patients with hereditary angioedema by age and gender. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Age groups
- 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.
Key inclusion criteria (1 listed)
- Documented diagnosis of hereditary angioedema due to C1 inhibitor deficiency aged between 18 and 65 years (for the group of patients)
Key exclusion criteria (4 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Heart rate
Time frame: Baseline
Changes in the heart rate (beats per minute) from resting to SECPT condition
Systolic arterial pressure
Time frame: Baseline
Changes in the systolic blood pressure (mmHg) from resting to SECPT condition
Diastolic arterial pressure
Time frame: Baseline
Changes in the systolic blood pressure (mmHg) from resting to SECPT condition
Visual Analogue Scale of perceived stress
Time frame: Baseline
Changes in the perceived stress due to SECP. Scores ranges from 0 (no stress) to 100 (worst stress possible)
Concentration of inflammatory cytokines
Time frame: Baseline
Changes in the concentration of inflammatory cytokines (pg/ml) due to SECPT
Concentration of plasma cathecolamines
Time frame: Baseline
Changes in the concentration of plasma cathecolamines (pg/ml) due to SECPT
6 secondary outcomes
Hospital Anxiety and Depression Scale
Time frame: Baseline
Perceived Stress Scale (PSS-10)
Time frame: Baseline
Multidimensional Assessment of Interoceptive Awareness Version 1
Time frame: Baseline
Body Appreciation Scale-2 (BAS-2)
Time frame: Baseline
Functionality Appreciation Scale (FAS)
Time frame: Baseline
Pain Catastrophizing Scale (PCS)
Time frame: Baseline
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2024.
- Derived from this study: PubMed 41573571De Maria B, Ranucci L, Gino C, Cesoni Marcelli A, Zingale LC, Zulueta A, Dalla Vecchia LA, Gorini A, Perego F. Functional physiological, psychological, and biochemical reactivity to socially evaluated cold pressor test in hereditary angioedema patients (FRoSEn). Front Immunol. 2026 Jan 7;16:1736589. doi: 10.3389/fimmu.2025.1736589. eCollection 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hereditary Angioedema, run by Istituti Clinici Scientifici Maugeri SpA at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Heart rate (time frame: Baseline). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06414252, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 May 2024.