Neurobehavioral Correlates of Caffeine on Anxiety, Avoidance and Interoception in Healthy Individuals and Panic Disorder.

Healthy Clinical Trial

— BINCAP  

Official title:

Adenosine Receptors From Genes to Behavior: Neurobehavioral Correlates of Caffeine on Anxiety, Avoidance, Decision-Making and Interoception in Healthy Individuals and Panic Disorder.

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06145490
• Other study ID #: 2023-02915-02
• Status: Not yet recruiting
• Phase: N/A
• Start date: August 2024
• Est. completion date: March 2025

Study information

• Verified date: May 2024
• Source: Uppsala University
• Contact: Andreas Frick, PhD
• Phone: +46736292771
• Email: andreas.frick[@]uu.se
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The current study is a placebo-controlled, double-blind, randomized controlled study using a cross-over design, including Healthy Controls (HC) and participants with Panic Disorder (PD).

The primary aim of the study is to investigate the neural correlates and behavioral effects of caffeine (versus placebo), and its impact on emotional reactivity, decision-making, and interoception, and compare the effects in individuals with PD vs HCs. Subjective anxiety and the occurrence of panic attacks will also be measured. Multimodal neuroimaging methods, such as structural and functional MRI, will be used to address the aims of the study.

Emotional reactivity, emotional decision-making and interoception will be measured with experimental tasks in a 7 Tesla (7T) magnetic resonance (MR) scanner, jointly with measures of skin conductance, heart rate, respiratory rate, and self-reported ratings of anxiety and interoception.

Emotional reactivity will be assessed using emotional and neutral faces. Emotional decision-making will be assessed with an approach-avoidance conflict task. Changes in interoception (bodily sensation, such as pulse and respiration) will be explored using a task in which participants are asked to focus on their breathing or an external stimulus. Caffeine effects on brain resting-state activity will also be assessed. All tasks will be conducted while in the 7T MR scanner.

A secondary aim of the study is to examine the impact of genetic variability in the adenosine A2A receptor (ADORA2A) genotype (e.g., rs5751876 T/T) on the effects of caffeine (vs placebo), as ADORA2A genotype has previously been associated with elevated caffeine-induced anxiety.

Description:

Given the novelty of the intended study and the lack of previous neuroimaging and emotion-related behavioral studies on caffeine effects in HCs and PD, analyses will be exploratory without directed hypotheses.

It is intended to conduct between-group analyses (HCs vs PD) in the two conditions (caffeine versus placebo), as well as within-group analyses in HCs and PD separately. Between-group analyses will also be conducted between individuals with different ADORA2A genotypes.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 100
• Est. completion date: March 2025
• Est. primary completion date: March 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Panic Disorder group (PD): Primary diagnosis of Panic Disorder.

• Healthy control group (HCs): No current or history of psychiatric disorders.

• All participants (PD and HCs): Weekly caffeine consumption = 300 mg.

Exclusion Criteria:

• Weekly caffeine consumption = 300 mg.

• Thoracic or head surgery, or any other surgery or metallic implanted devices not compatible with the safety standards for 7T MR scanner.

• History of severe psychiatric disorder (e.g., schizophrenia).

• Somatic or neurological conditions (e.g., hypertension and heart condition).

• Ongoing treatment with psychotropic medication or treatment with psychotropic medication which has been discontinued within 2 months.

• Other ongoing treatments that may confound the results.

• Current drug or alcohol abuse/dependency.

• Habitual nicotine use.

• Uncorrected visual or hearing impairment.

• Pregnancy.

Related Conditions & MeSH terms

• Healthy
• Panic Disorder

Intervention

Dietary Supplement:
• Caffeine
Caffeine capsule 250 mg, oral intake

Drug:
• Placebo
Placebo capsule, oral intake

Locations

Country	Name	City	State
Sweden	Uppsala University, Department of Medical Sciences, Psychiatry	Uppsala

Sponsors (1)

Lead Sponsor	Collaborator
Uppsala University

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Expectancy ratings	Participants will be asked to report if they believed they received placebo or caffeine and how certain they are on a scale from 0-100% before capsule intake and after completing the MR-session.	Session 1 (day 1)
Other	Expectancy ratings	Participants will be asked to report if they believed they received placebo or caffeine and how certain they are on a scale from 0-100% before capsule intake and after completing the MR-session.	Session 2 (day 2; minimum of 36 hours after session/day 1)
Other	Panic Disorder Severity Scale (PDSS)	PDSS is a self-reported questionnaire that assesses the severity of Panic Disorder; range 0-28, higher scores indicating more severe symptoms.	1-7 days prior to session 1 (internet)
Other	Body Sensations Questionnaire (BSQ)	BSQ assesses body sensations present during aversive situations; range 17-85, higher scores indicating higher levels of body sensations.	1-7 days prior to session 1 (internet)
Other	Multidimensional Assessment of Interoceptive Awareness (MAIA-2)	MAIA-2 is an 8-scale state-trait questionnaire with 37 items to measure multiple dimensions of interoception by self- report. The score of each scale is the the average of the items on each scale. Higher mean scores indicate higher levels of the measured dimensions (Noticing, Not-Distracting, Not-Worrying, Attention Regulation, Emotional Awareness,Self-Regulation, Body Listening, and Trust) on a scale from 0-5 (0=never- 5=always), respectively.	1-7 days prior to session 1 (internet)
Other	Anxiety Sensitivity Index (ASI)	ASI assesses anxiety sensitivity; range 0-64, higher scores indicating higher anxiety sensitivity.	1-7 days prior to session 1 (internet)
Other	Spielberger State-Trait Anxiety Inventory (STAI-T)	STAI-T is a self-rated questionnaire assessing trait anxiety; range 20-80, higher scores represent higher levels of trait anxiety.	1-7 days prior to session 1 (internet)
Other	Caffeine Expectancy Questionnaire (CaffEQ)	CaffEQ is a self-rated questionnaire that assesses expected effect of caffeine intake.	1-7 days prior to session 1 (internet)
Primary	Task-related BOLD fMRI signal	Task-related BOLD (blood-oxygen-level-dependent) fMRI (functional magnetic resonance imaging) signal will be collected through a 7T MR scanner, starting approximately 30 minutes after oral intake of caffeine or placebo pill. Tasks: Emotional reactivity, Approach-Avoidance Conflict Task, Interoception, Resting-state fMRI.	Session 1 (day 1)
Primary	Task-related BOLD fMRI signal	Task-related BOLD (blood-oxygen-level-dependent) fMRI (functional magnetic resonance imaging) signal will be collected through a 7T MR scanner, starting approximately 30 minutes after oral intake of caffeine or placebo pill. Tasks: Emotional reactivity, Approach-Avoidance Conflict Task, Interoception, Resting-state fMRI.	Session 2 (day 2; minimum of 36 hours after session/day 1)
Primary	Self-reported anxiety	Anxiety will be assessed before capsule intake (either caffeine or placebo), 20 minutes after intake, after each task, and during the interoception task measured with self-reported ratings, on a scale from 0-100 (0= no anxiety - 100= extreme anxiety).	Session 1 (day 1)
Primary	Self-reported anxiety	Anxiety will be assessed before capsule intake (either caffeine or placebo), 20 minutes after intake, after each task, and during the interoception task measured with self-reported ratings, on a scale from 0-100 (0= no anxiety - 100= extreme anxiety).	Session 2 (day 2; minimum of 36 hours after session/day 1)
Primary	Self-reported interoceptive awareness	Interoceptive awareness will be assessed before capsule intake (either caffeine or placebo), 20 minutes after intake, after each task in the MR scanner, and during the interoception task, measured with self-reported ratings on a scale from 0-100 (0= no awareness - 100= extreme awareness).	Session 1 (day 1)
Primary	Self-reported interoceptive awareness	Interoceptive awareness will be assessed before capsule intake (either caffeine or placebo), 20 minutes after intake, after each task in the MR scanner, and during the interoception task, measured with self-reported ratings on a scale from 0-100 (0= no awareness - 100= extreme awareness).	Session 2 (day 2; minimum of 36 hours after session/day 1)
Primary	Self-reported interoceptive functional impairment	Interoceptive functional impairment will be assessed before capsule intake (either caffeine or placebo), 20 minutes after intake, after each task, and during the interoception task, measured with self-reported ratings on a scale from 0-100 (0= no impairment - 100= extreme impairment).	Session 1 (day 1)
Primary	Self-reported interoceptive functional impairment	Interoceptive functional impairment will be assessed before capsule intake (either caffeine or placebo), 20 minutes after intake, after each task, and during the interoception task, measured with self-reported ratings on a scale from 0-100 (0= no impairment - 100= extreme impairment).	Session 2 (day 2; minimum of 36 hours after session/day 1)
Primary	Skin conductance responses (SCR)	Skin conductance responses will be used to assess emotional reactivity at the physiological level to emotional stimuli vs neutral stimuli (faces).	Session 1 (day 1)
Primary	Skin conductance responses (SCR)	Skin conductance responses will be used to assess emotional reactivity at the physiological level to emotional stimuli vs neutral stimuli (faces).	Session 2 (day 2; minimum of 36 hours after session/day 1)
Primary	Occurrence of panic attacks	The occurrence of panic attacks will be assessed according to the Diagnostic Statistical Manual (DSM-5) criteria for panic attacks and will be coded dichotomous as "present" or "not present".	Session 1 (day 1)
Primary	Occurrence of panic attacks	The occurrence of panic attacks will be assessed according to the Diagnostic Statistical Manual (DSM-5) criteria for panic attacks and will be coded dichotomous as "present" or "not present".	Session 2 (day 2; minimum of 36 hours after session/day 1)
Secondary	Structural brain data, T1-w sMRI	Structural brain changes will be analyzed through T1-weighted sMRI (structural magnetic resonance imaging).	Session 1 (day 1)
Secondary	Structural brain data, T1-w sMRI	Structural brain changes will be analyzed through T1-weighted sMRI (structural magnetic resonance imaging).	Session 2 (day 2; minimum of 36 hours after session/day 1)
Secondary	Heart rate variability	Heart rate variability (HRV) will be assessed by using a 7T MR-compatible heart rate band, during the whole MR scanner time.	Session 1 (day 1)
Secondary	Heart rate variability	Heart rate variability (HRV) will be assessed by using a 7T MR-compatible heart rate band, during the whole MR scanner time.	Session 2 (day 2; minimum of 36 hours after session/day 1)
Secondary	Respiratory rate	Respiratory or breathing rates will be assessed during the whole MR scanner time.	Session 1 (day 1)
Secondary	Respiratory rate	Respiratory or breathing rates will be assessed during the whole MR scanner time.	Session 2 (day 2; minimum of 36 hours after session/day 1)