Clinical trial NCT03419858: The Role of Opioidergic Systems in Breathing Based Analgesia
Official title: The Role of Endogenous Opioidergic Systems in Breathing Based Analgesia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Pain
Keywords: Pain
Slow-Breathing
Mindfulness
Opioids
Placebo
Lead sponsor: University of California, San Diego
Sponsor class: OTHER
First posted: 2018-02-05
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: The study employed a double blind 3x2x2 crossover factorial design. Baseline pain intensity and pain unpleasantness ratings were assessed using visual analog scales (11 point) obtained before and after four, 5-minute noxious heat stimulation series (49°C). Study volunteers (20/group; 60 total) were randomized and subsequently participated in a four session (20min/session) mindfulness meditation, placebo-meditation, or slow-breathing training regimen. After training completion, subjects reported to the Wake Forest Clinical Research Unit to test the study hypotheses across two separate experimental sessions. Half of the study volunteers (n=10) from each group were administered naloxone (opioid antagonist; 0.15 mg/kg bolus+ 0.1mg/kg/hour infusion) and in the subsequent session were administered IV placebo-saline and vice versa.
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this psychophysical and pharmacologic study is to determine if slow-breathing induced pain relief is mediated by endogenous opioids in response to intravenous (IV) administration of the opioid antagonist naloxone during noxious heat stimulation. We were also interested in disentangling the endogenous analgesic mechanisms supporting mindfulness-based analgesia.

Detailed description: The proposed study will employ a graded analytical approach to compare mindfulness to placebo-meditation and a slow-breathing exercise in response to double-blind intravenous administration (IV) of naloxone/placebo-saline and noxious heat stimulation. The aim of this study is to determine if slow-breathing induced analgesia is associated with the release of endogenous opioids. The proposed study will disentangle the specific stage of cognitive and/or respiration-based involvement (if any) of opioidergically mediated pain relief, a critical step in identifying the specific analgesic mechanisms corresponding to mindfulness based cognitive techniques.

Eligibility criteria: Inclusion Criteria:

* Normal volunteers with no history of chronic pain problems
* Volunteers had no prior meditation experience
* Volunteers could be male and non-pregnant females.
* Volunteers of all ethnic backgrounds were included.

Exclusion Criteria:

* Female volunteers could not be pregnant.
* They could not be taking opioids or antidepressants.
* Subjects with a repeated history of syncope, loss of consciousness, light headedness, nausea, dizziness, or vomiting in response to needles or blood could not participate in the study.
* Subject could not be using exogenous opiates for the complete duration of the study.

Primary outcomes:
measure: Change in Visual Analog Scale Pain intensity and Unpleasantness ratings as a function of each respective cognitive manipulations and activation in response to naloxone and/or saline.
timeFrame: Up to 3 weeks
Secondary outcomes:
measure: Respiration Rate Measures
timeFrame: Up to 3 weeks
measure: State Anxiety Inventory
timeFrame: up to 3 weeks
measure: Pain Catastrophizing Scale (PCS)
timeFrame: up to 3 weeks
measure: Cohen Perceived Stress Scale (CPS)
timeFrame: up to 3 weeks
measure: Treatment Effectiveness Scale
timeFrame: up to 3 weeks
measure: Attitude Toward Treatment Scale (ATTS)
timeFrame: up to 3 weeks
measure: Center for Epidemiological Studies Depression Scale (CES-D)
timeFrame: up to 3 weeks
measure: Stress-Level Visual Analogue Scale
timeFrame: up to 3 weeks
measure: Naloxone Symptom Assessments
timeFrame: Up to 3 weeks
Other outcomes:
Locations:
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
Study officials:
affiliation: Wake Forest University Health Sciences
name: Fadel Zeidan, PhD
role: PRINCIPAL_INVESTIGATOR
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