Clinical trial NCT05261594: Effects of Caffeine on Anxiety, Emotional Processing, Approach-avoidance Behavior, and Interoception in Panic Disorder
Official title: Effects of Caffeine on Anxiety, Emotional Processing, Approach-avoidance Behavior, and Interoception in Panic Disorder - a Double Blind Randomized Controlled Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Panic Disorder
Healthy
Lead sponsor: Uppsala University
Sponsor class: OTHER
First posted: 2022-03-02
Enrollment: 83
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: The study entails two sessions and uses a crossover design. Participants will be randomized to start with either the caffeine condition or the placebo condition. Participants will complete the second session with the other condition (the condition not allocated to in session 1).

The study includes two arms: (a) participants with Panic disorder (estimated n=50; actual n=30) and (b) healthy controls (estimated n=50; actual n=53). Both arms (Panic disorder and healthy controls) will complete both conditions (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 participants with Panic disorder and healthy controls.

The study's primary aim is to investigate the effects of caffeine (vs placebo) on self-reported anxiety and its impact on emotional reactivity and goal-directed behavior in individuals with Panic disorder (vs healthy controls). Emotional reactivity will be measured with self-reported emotions and skin conductance responses. Caffeine-induced effects on goal-directed behavior will be assessed using an approach-avoidance conflict paradigm and an effort-allocation task. The occurrence of panic attacks and panic-related symptoms will also be measured. Furthermore, the link between a genotype of ADORA2A (rs5751876 T/T) previously associated with caffeine-induced anxiety, and the anxiogenic effects of caffeine will also be explored. In addition, caffeine-induced changes in attention to interoceptive stimuli (bodily sensation such as pulse and respiration) and anxiety elicited by attention to interoceptive stimuli will be explored. A secondary aim is to examine the potential caffeine-induced effects and the impact of genetic variation in healthy participants (caffeine vs placebo).

Detailed description: Hypotheses

Self-reported anxiety during resting state

* Participants with Panic disorder will report higher resting-state levels of anxiety and negative emotions during the caffeine condition vs the placebo condition.
* Participants with Panic disorder will report higher resting-state levels of caffeine-induced (caffeine \> placebo) anxiety and negative emotions compared to healthy subjects.

Panic attacks

* The occurrence of panic attacks and panic-related symptoms will be higher among participants with Panic disorder than in healthy controls in both conditions (caffeine and placebo).

Genetic variation

* Carriers of adenosine A2A receptor (i.e., ADORA2A) polymorphism (rs5751876 T/T) will report higher levels of caffeine-induced (caffeine \>placebo) anxiety and negative emotions, in both individuals with Panic disorder and healthy participants.

Attention to interoceptive stimuli and associated anxiety

* Participants with Panic disorder will report higher levels of attention towards interoceptive stimuli in the caffeine condition (vs placebo).
* Participants with Panic disorder will report higher levels of self-reported anxiety associated with experiencing interoceptive stimuli during the caffeine condition (vs placebo).
* Participants with Panic disorder will report higher levels of self-reported attention to interoceptive stimuli and anxiety associated with experiencing interoceptive stimuli compared to healthy participants, both in general (placebo condition) and after caffeine intake (caffeine vs placebo).

Exploratory research questions

Analyses of emotional reactivity, the approach-avoidance conflict task, and the effort-allocation task will be exploratory without directed hypotheses, due to lack of previous research on the effects of caffeine in patients with Panic disorder on these tasks. We will also conduct exploratory analyses to explore if 150 mg of caffeine (vs placebo) affect self-reported levels of positive emotions in patients with Panic disorder and healthy controls.

Eligibility criteria: Inclusion Criteria:

Panic disorder group: Primary diagnosis of panic disorder.

Healthy control group: No current or history of psychiatric disorders.

All participants (Panic disorder and healthy): Weekly caffeine consumption ≤ 300 mg.

Exclusion Criteria:

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: Self-reported anxiety
timeFrame: Session 1 (day 1)
measure: Self-reported anxiety
timeFrame: Session 2 (minimum of 36 hours after Session 1 (day 1) maximum of 14 days after Session 1 (day 1))
Secondary outcomes:
measure: Self-reported emotions
timeFrame: Session 1 (day 1)
measure: Self-reported emotions
timeFrame: Session 2 (minimum of 36 hours after Session 1 (day 1) maximum of 14 days after Session 1 (day 1))
measure: Skin conductance responses (SCR)
timeFrame: Session 1 (day 1)
measure: Skin conductance responses (SCR)
timeFrame: Session 2 (minimum of 36 hours after Session 1 (day 1) maximum of 14 days after Session 1 (day 1))
measure: Approach-avoidance behavior
timeFrame: Session 1 (day 1)
measure: Approach-avoidance behavior
timeFrame: Session 2 (minimum of 36 hours after Session 1 (day 1) maximum of 14 days after Session 1 (day 1))
measure: Effort-allocation
timeFrame: Session 1 (day 1)
measure: Effort-allocation
timeFrame: Session 2 (minimum of 36 hours after Session 1 (day 1) maximum of 14 days after Session 1 (day 1))
measure: Occurrence of panic attack
timeFrame: Session 1 (day 1)
measure: Occurrence of panic attack
timeFrame: Session 2 (minimum of 36 hours after Session 1 (day 1) maximum of 14 days after Session 1 (day 1))
measure: Panic symptoms
timeFrame: Session 1 (day 1)
measure: Panic symptoms
timeFrame: Session 2 (minimum of 36 hours after Session 1 (day 1) maximum of 14 days after Session 1 (day 1))
measure: Attention to interoceptive stimuli
timeFrame: Session 1 (day 1)
measure: Attention to interoceptive stimuli
timeFrame: Session 2 (minimum of 36 hours after Session 1 (day 1) maximum of 14 days after Session 1 (day 1))
measure: Anxiety associated with attention to interoceptive stimuli
timeFrame: Session 1 (day 1)
measure: Anxiety associated with attention to interoceptive stimuli
timeFrame: Session 2 (minimum of 36 hours after Session 1 (day 1) maximum of 14 days after Session 1 (day 1))
Other outcomes:
measure: Expectancy ratings
timeFrame: Session 1 (day 1)
measure: Expectancy ratings
timeFrame: Session 2 (minimum of 36 hours after Session 1 (day 1) maximum of 14 days after Session 1 (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 (via internet)
measure: Multidimensional Assessment of Interoceptive Awareness (MAIA-2)
timeFrame: 1-7 days prior to session 1 (via internet)
measure: Anxiety Sensitivity Index (ASI)
timeFrame: 1-7 days prior to session 1 (via internet)
measure: Spielberger State-Trait Anxiety Inventory (STAI-T)
timeFrame: 1-7 days prior to session 1 (via internet)
measure: Caffeine Expectancy Questionnaire (CaffEQ)
timeFrame: 1-7 days prior to session 1 (via internet)
Locations:
city: Uppsala
country: Sweden
facility: Uppsala university, Department of Medical Sciences, Psychiatry
Study officials:
affiliation: Uppsala University
name: Andreas Frick, PhD
role: PRINCIPAL_INVESTIGATOR
References: