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

NCT06145490 | Completed

• 1 other identifier: 2023-02915-02
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Panic Disorder; Healthy

Outcome Measures

Primary Outcomes (12)

• 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)

• 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)

• 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)

• 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)

• 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)

• 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)

• 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)

• 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)

• 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)

• 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)

• 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)

• 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 Outcomes (6)

• Structural brain data, T1-w sMRI

  Session 1 (day 1)

• Structural brain data, T1-w sMRI

  Session 2 (day 2; minimum of 36 hours after session/day 1)

• Heart rate variability

  Session 1 (day 1)

• Heart rate variability

  Session 2 (day 2; minimum of 36 hours after session/day 1)

• Respiratory rate

  Session 1 (day 1)

Other Outcomes (8)

• Expectancy ratings

  Session 1 (day 1)

• Expectancy ratings

  Session 2 (day 2; minimum of 36 hours after session/day 1)

• Panic Disorder Severity Scale (PDSS)

  1-7 days prior to session 1 (internet)

Study Arms (2)

Panic Disorder

OTHER

Participants will be randomized to start with either the caffeine condition or the placebo condition. Participants will complete session 2 with the other condition (condition not allocated to in session 1).

Dietary Supplement: Caffeine; Drug: Placebo

Healthy controls

OTHER

Participants will be randomized to start with either the caffeine condition or the placebo condition. Participants will complete session 2 with the other condition (condition not allocated to in session 1).

Dietary Supplement: Caffeine; Drug: Placebo

Interventions

Caffeine DIETARY_SUPPLEMENT

Caffeine capsule 250 mg, oral intake

Healthy controls; Panic Disorder

Placebo DRUG

Placebo capsule, oral intake

Healthy controls; Panic Disorder

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Uppsala University: lead

Study Sites (2)

National 7T Facility - Lunds universitet

Lund, Sweden

Location

Uppsala University, Department of Medical Sciences, Psychiatry

Uppsala, 75185, Sweden

Location

MeSH Terms

Conditions

Panic Disorder

Interventions

Caffeine

Condition Hierarchy (Ancestors)

Anxiety Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Xanthines; Alkaloids; Heterocyclic Compounds; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Andreas Frick, PhD

  Uppsala University, Department of Medical Sciences, Psychiatry

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The study entails two sessions with a cross-over design. Participants will be randomized to start with either the caffeine condition or the placebo condition. The study includes two arms: (a) participants with Panic Disorder (anticipated n = 50) and (b) Healthy controls (anticipated n = 50). Both arms (Panic Disorder and Healthy controls) will complete both conditions with the two sessions (caffeine and placebo condition) in randomized order.

Study Record Dates

• First Submitted: November 17, 2023
• First Posted: November 24, 2023
• Study Start: October 29, 2024
• Primary Completion: May 15, 2025
• Study Completion: May 15, 2025
• Last Updated: February 27, 2026

Record last verified: 2026-02

Locations

SE (2)