Effects of Caffeine on Anxiety, Emotional Processing, Approach-avoidance Behavior, and Interoception in Panic Disorder

Healthy Clinical Trial

Official title:

Effects of Caffeine on Anxiety, Emotional Processing, Approach-avoidance Behavior, and Interoception in Panic Disorder - a Double Blind Randomized Controlled Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05261594
• Other study ID #: 2019-06451
• Status: Completed
• Phase: N/A
• Start date: March 16, 2022
• Est. completion date: March 19, 2023

Study information

• Verified date: April 2023
• Source: Uppsala University
• Contact: n/a
• 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 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 83
• Est. completion date: March 19, 2023
• Est. primary completion date: March 19, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Healthy
• Panic Disorder

Intervention

Dietary Supplement:
• Caffeine
Caffeine capsule 150 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 that they received placebo or caffeine and how certain they are on a scale from 0-100%	Session 1 (day 1)
Other	Expectancy ratings	Participants will be asked to report if they believed that they received placebo or caffeine and how certain they are on a scale from 0-100%	Session 2 (minimum of 36 hours after Session 1 (day 1) maximum of 14 days after Session 1 (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 (via 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 on 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 (via 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 (via 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 (via 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 (via internet)
Primary	Self-reported anxiety	Anxiety will be assessed before capsule (caffeine/placebo) intake, 30 minutes after intake during rest, and after each task 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 (caffeine/placebo) intake, 30 minutes after intake during rest, and after each task with self-reported ratings on a scale from 0-100 (0=no anxiety - 100=extreme anxiety).	Session 2 (minimum of 36 hours after Session 1 (day 1) maximum of 14 days after Session 1 (day 1))
Secondary	Self-reported emotions	Self-reported emotions (fear, bodily discomfort, negative feelings and positive feelings) will be assessed before capsule (caffeine/placebo) intake, 30 minutes after intake during rest, and after each task with self-reported ratings on a scale from 0-100 (0=none - 100=extreme).	Session 1 (day 1)
Secondary	Self-reported emotions	Self-reported emotions (fear, bodily discomfort, negative feelings and positive feelings) will be assessed before capsule (caffeine/placebo) intake, 30 minutes after intake during rest, and after each task with self-reported ratings on a scale from 0-100 (0=none - 100=extreme).	Session 2 (minimum of 36 hours after Session 1 (day 1) maximum of 14 days after Session 1 (day 1))
Secondary	Skin conductance responses (SCR)	SCR:s will be used to assess emotional reactivity at the physiological level to emotional stimuli vs neutral stimuli (faces).	Session 1 (day 1)
Secondary	Skin conductance responses (SCR)	SCR:s will be used to assess emotional reactivity at the physiological level to emotional stimuli vs neutral stimuli (faces).	Session 2 (minimum of 36 hours after Session 1 (day 1) maximum of 14 days after Session 1 (day 1))
Secondary	Approach-avoidance behavior	Approach-avoidance behavior will be assessed through an approach-avoidance incentive conflict task.	Session 1 (day 1)
Secondary	Approach-avoidance behavior	Approach-avoidance behavior will be assessed through an approach-avoidance incentive conflict task.	Session 2 (minimum of 36 hours after Session 1 (day 1) maximum of 14 days after Session 1 (day 1))
Secondary	Effort-allocation	Effort-allocation for rewards will be assessed using an effort-allocation task.	Session 1 (day 1)
Secondary	Effort-allocation	Effort-allocation for rewards will be assessed using an effort-allocation task.	Session 2 (minimum of 36 hours after Session 1 (day 1) maximum of 14 days after Session 1 (day 1))
Secondary	Occurrence of panic attack	The occurrence of a panic attacks will be assessed according to the Diagnostical Statistical Manual (DSM-5) criteria for panic attacks and will be coded dichotomous as "Present" or "Not present".	Session 1 (day 1)
Secondary	Occurrence of panic attack	The occurrence of a panic attacks will be assessed according to the Diagnostical Statistical Manual (DSM-5) criteria for panic attacks and will be coded dichotomous as "Present" or "Not present".	Session 2 (minimum of 36 hours after Session 1 (day 1) maximum of 14 days after Session 1 (day 1))
Secondary	Panic symptoms	Panic symptoms will be assessed by counting the number of DSM-5- panic attack symptoms reported by the participant.	Session 1 (day 1)
Secondary	Panic symptoms	Panic symptoms will be assessed by counting the number of DSM-5- panic attack symptoms reported by the participant.	Session 2 (minimum of 36 hours after Session 1 (day 1) maximum of 14 days after Session 1 (day 1))
Secondary	Attention to interoceptive stimuli	Attention to interoceptive stimuli will be assessed using self-reported ratings on a scale from 0-100 (0=no attention - 100= full attention). Interoceptive stimuli are defined as bodily sensation such as pulse and respiration.	Session 1 (day 1)
Secondary	Attention to interoceptive stimuli	Attention to interoceptive stimuli will be assessed using self-reported ratings on a scale from 0-100 (0=no attention - 100= full attention). Interoceptive stimuli are defined as bodily sensation such as pulse and respiration.	Session 2 (minimum of 36 hours after Session 1 (day 1) maximum of 14 days after Session 1 (day 1))
Secondary	Anxiety associated with attention to interoceptive stimuli	Self-reported ratings of anxiety associated with attention to interoceptive stimuli (bodily sensation such as pulse and respiration) will be assessed using self reported ratings on a scale from (0= no anxiety - 100 = extreme anxiety)	Session 1 (day 1)
Secondary	Anxiety associated with attention to interoceptive stimuli	Self-reported ratings of anxiety associated with attention to interoceptive stimuli (bodily sensation such as pulse and respiration) will be assessed using self reported ratings on a scale from (0= no anxiety - 100 = extreme anxiety)	Session 2 (minimum of 36 hours after Session 1 (day 1) maximum of 14 days after Session 1 (day 1))