Study of Pain Processing in Subjects Suffering From Obstructive Sleep Apnea

NCT00672737 | Completed Results DMC

• 2 other identifiers: SU-01222008-98510374
• Study Type: observational
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

We would like to test the effect of opioid medication on pain sensitivity in subjects who have been diagnosed with a sleep disorder called Obstructive Sleep Apnea (OSA) compared to other subjects without OSA. Patients with OSA may have an altered sensitivity to the sedative, analgesic, and respiratory depressant effects of opioids.

Conditions

Sleep Apnea, Obstructive

Outcome Measures

Primary Outcomes (4)

• Experimental Cold-induced Pain - IGFBP-1

  The effect of insulin growth factor binding protein-1 (IGFBP-1), a serum hypoxia marker, on the change of cold-induced pain thresholds under remifentanil was estimated using a mixed linear regression model. The results were expressed by the estimated beta (95% CI), indicating how much the change in the cold pain threshold (expressed in seconds) under remifentanil, was altered per unit of change in the IGFBP-1. For example, for every 1-pg/mL increase in the serum level of IGFBP-1, cold pain threshold will additionally increase by 0.0025 seconds for every 1-mcg/mL increase in the plasma level of remifentanil.

  2 to 3 weeks

• Experimental Heat-induced Pain - IGFBP-1

  The effect of arterial oxyhemoglobin desaturation during sleep (chronic intermittent hypoxia expressed by insulin growth factor binding protein-1 (IGFBP-1), a serum hypoxia marker, on the change of heat-induced pain thresholds under remifentanil was estimated using a mixed linear regression model. The results were expressed by the estimated betas (95% CI), indicating how much the change in the heat pain threshold (expressed in C') under remifentanil, was altered per unit of change in the IGFBP-1. For example, for every 1-pg/mL increase in serum level of IGFBP-1, the heat pain threshold will additionally decrease by 0.0001 'C for every 1-mcg/mL increase in the plasma level of remifentanil.

  2 to 3 weeks

• Experimental Cold-induced Pain - SaO2

  The effect of arterial oxyhemoglobin desaturation during sleep (chronic intermittent hypoxia expressed by nadir SaO2 during polysomnography) on the change of cold-induced pain thresholds under remifentanil was estimated using a mixed linear regression model. The results were expressed by the estimated betas (95% CI), indicating how much the change in the cold pain threshold (expressed in seconds) under remifentanil, was altered per unit of change in the SaO2. For example, for every 1-%-absolute decrease in the nadir SaO2, the cold pain threshold will additionally increase by 0.9694 seconds for every 1-mcg/mL increase in the plasma level of remifentanil.

  2 to 3 weeks

• Experimental Heat-induced Pain - SaO2

  The effect of arterial oxyhemoglobin desaturation during sleep (chronic intermittent hypoxia expressed by nadir SaO2 during polysomnography), on the change of heat-induced pain thresholds under remifentanil was estimated using a mixed linear regression model. The results were expressed by the estimated betas (95% CI), indicating how much the change in the heat pain threshold (expressed in C') under remifentanil, was altered per unit of change in the SaO2. For example, for every 1-%-absolute decrease in the nadir SaO2, the heat pain threshold will additionally increase by 0.0172 'C for every 1-mcg/mL increase in the plasma level of remifentanil.

  2 to 3 weeks

Study Arms (1)

Males at risk for OSA

Males at risk for obstructive sleep apnea were invited to have a "sleep study" either at home or at Stanford Sleep Center. A week after their sleep study (Polysomnography), all volunteers underwent quantitative sensory testing in the laboratory, during which their pain thresholds and tolerances to heat (Heat pain threshold and tolerance) and cold (Cold pain threshold and tolerance) stimuli were assessed, under two different concentrations (1 and 2 mcg/mL, in randomized order) of remifentanil, a short-acting opioid, given as a computer-controlled infusion.

Drug: Remifentanil; Procedure: Cold pain threshold and tolerance; Device: Heat pain threshold and tolerance; Procedure: Polysomnography

Interventions

Remifentanil DRUG

Remifentanil was administered as a computer-controlled infusion, targeting two different effect site concentrations, 1 and 2 mcg/mL, in randomized order.

Males at risk for OSA

Cold pain threshold and tolerance PROCEDURE

Ice water was used to assess cold-related pain threshold and tolerance, defined as the time that the volunteers could keep their hands in the water before they started feeling pain or this feeling becomes unbearable, for threshold and tolerance, respectively.

Males at risk for OSA

Heat pain threshold and tolerance DEVICE

TSAII Neuroanalyzer (Medoc Advanced Medical Systems, Durham, NC), was used to assess the heat-related pain and tolerance of the volunteers defined as the respective temperatures where they started feeling as painful or unbearable.

Males at risk for OSA

Polysomnography PROCEDURE

All volunteers underwent a polysomnography study at home or at Stanford Sleep Center, approximately one week before their experimental pain assessment in the laboratory

Also known as: sleep study

Males at risk for OSA

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Males at risk for obstructive sleep apnea (OSA). We invited male volunteers (18 55 years old) with a history of habitual snoring and/or a formal diagnosis of OSA to participate in a study evaluating sleep and experimental pain processing.

Sponsors & Collaborators

• Stanford University: lead

Study Sites (1)

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

Related Publications (1)

• Doufas AG, Tian L, Padrez KA, Suwanprathes P, Cardell JA, Maecker HT, Panousis P. Experimental pain and opioid analgesia in volunteers at high risk for obstructive sleep apnea. PLoS One. 2013;8(1):e54807. doi: 10.1371/journal.pone.0054807. Epub 2013 Jan 29.

  PMID: 23382975 RESULT

MeSH Terms

Conditions

Sleep Apnea, Obstructive

Interventions

Remifentanil; Drug Tolerance

Condition Hierarchy (Ancestors)

Sleep Apnea Syndromes; Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Propionates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pharmacological Phenomena; Pharmacological and Toxicological Phenomena; Physiological Phenomena

Results Point of Contact

• Title: Anthony Doufas, MD, PhD
• Organization: Stanford University

agdoufas@stanford.edu

(650) 498-7699

Study Officials

• Anthony Doufas

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: May 2, 2008
• First Posted: May 6, 2008
• Study Start: February 1, 2008
• Primary Completion: August 1, 2010
• Study Completion: August 1, 2010
• Last Updated: August 7, 2017
• Results First Posted: August 7, 2017

Record last verified: 2017-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)