Clinical trial NCT06145490: Neurobehavioral Correlates of Caffeine on Anxiety, Avoidance and Interoception in Healthy Individuals and Panic Disorder.
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.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Panic Disorder
Healthy
Lead sponsor: Uppsala University
Sponsor class: OTHER
First posted: 2023-11-24
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: 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.
Primary purpose: BASIC_SCIENCE

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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Task-related BOLD fMRI signal
timeFrame: Session 1 (day 1)
measure: Task-related BOLD fMRI signal
timeFrame: Session 2 (day 2; minimum of 36 hours after session/day 1)
measure: Self-reported anxiety
timeFrame: Session 1 (day 1)
measure: Self-reported anxiety
timeFrame: Session 2 (day 2; minimum of 36 hours after session/day 1)
measure: Self-reported interoceptive awareness
timeFrame: Session 1 (day 1)
measure: Self-reported interoceptive awareness
timeFrame: Session 2 (day 2; minimum of 36 hours after session/day 1)
measure: Self-reported interoceptive functional impairment
timeFrame: Session 1 (day 1)
measure: Self-reported interoceptive functional impairment
timeFrame: Session 2 (day 2; minimum of 36 hours after session/day 1)
measure: Skin conductance responses (SCR)
timeFrame: Session 1 (day 1)
measure: Skin conductance responses (SCR)
timeFrame: Session 2 (day 2; minimum of 36 hours after session/day 1)
measure: Occurrence of panic attacks
timeFrame: Session 1 (day 1)
measure: Occurrence of panic attacks
timeFrame: Session 2 (day 2; minimum of 36 hours after session/day 1)
Secondary outcomes:
measure: Structural brain data, T1-w sMRI
timeFrame: Session 1 (day 1)
measure: Structural brain data, T1-w sMRI
timeFrame: Session 2 (day 2; minimum of 36 hours after session/day 1)
measure: Heart rate variability
timeFrame: Session 1 (day 1)
measure: Heart rate variability
timeFrame: Session 2 (day 2; minimum of 36 hours after session/day 1)
measure: Respiratory rate
timeFrame: Session 1 (day 1)
measure: Respiratory rate
timeFrame: Session 2 (day 2; minimum of 36 hours after session/day 1)
Other outcomes:
measure: Expectancy ratings
timeFrame: Session 1 (day 1)
measure: Expectancy ratings
timeFrame: Session 2 (day 2; minimum of 36 hours after session/day 1)
measure: Panic Disorder Severity Scale (PDSS)
timeFrame: 1-7 days prior to session 1 (internet)
measure: Body Sensations Questionnaire (BSQ)
timeFrame: 1-7 days prior to session 1 (internet)
measure: Multidimensional Assessment of Interoceptive Awareness (MAIA-2)
timeFrame: 1-7 days prior to session 1 (internet)
measure: Anxiety Sensitivity Index (ASI)
timeFrame: 1-7 days prior to session 1 (internet)
measure: Spielberger State-Trait Anxiety Inventory (STAI-T)
timeFrame: 1-7 days prior to session 1 (internet)
measure: Caffeine Expectancy Questionnaire (CaffEQ)
timeFrame: 1-7 days prior to session 1 (internet)
Locations:
city: Lund
country: Sweden
facility: National 7T Facility - Lunds universitet
city: Uppsala
country: Sweden
facility: Uppsala University, Department of Medical Sciences, Psychiatry
Study officials:
affiliation: Uppsala University, Department of Medical Sciences, Psychiatry
name: Andreas Frick, PhD
role: PRINCIPAL_INVESTIGATOR
References: