Trial Outcomes & Findings for Study of Pain Processing in Subjects Suffering From Obstructive Sleep Apnea (NCT NCT00672737)

Results Overview

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.

Recruitment status

COMPLETED

Target enrollment

56 participants

Primary outcome timeframe

2 to 3 weeks

Results posted on

2017-08-07

Participant Flow

From January 2008 till March 2010, 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 at the Human Pain Laboratory in the Department of Anesthesiology at Stanford University.

We screened 167 male volunteers; 56 consented to participate to the study.

Participant milestones

Participant milestones
Measure	Male Volunteers at Risk for Sleep Apnea After approval from the Institutional Review Board and informed consent, we assessed cold and heat pain thresholds in volunteers after overnight polysomnography (PSG). We measured insulin growth factor binding protein-1 (IGFBP-1) a hypoxia-related serum marker. Pain tests were performed at baseline, placebo, and two effect site concentrations of remifentanil (1 and 2 mg/ml), an mu-opioid agonist. Linear mixed effects regression model was employed to evaluate the association of the lowest oxyhemoglobin saturation (SaO2) during sleep and IGFBP-1 with the changes in pain thresholds after remifentanil administration.
Overall Study STARTED	56
Overall Study COMPLETED	48
Overall Study NOT COMPLETED	8

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study of Pain Processing in Subjects Suffering From Obstructive Sleep Apnea

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Male Volunteers at Risk for Sleep Apnea n=53 Participants After approval from the Institutional Review Board and informed consent, we assessed cold and heat pain thresholds in volunteers after overnight polysomnography (PSG). We measured insulin growth factor binding protein-1 (IGFBP-1) a hypoxia-related serum marker. Pain tests were performed at baseline, placebo, and two effect site concentrations of remifentanil (1 and 2 mg/ml), an mu-opioid agonist. Linear mixed effects regression model was employed to evaluate the association of the lowest oxyhemoglobin saturation (SaO2) during sleep and IGFBP-1 with the changes in pain thresholds after remifentanil administration.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	53 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	36 years STANDARD_DEVIATION 11 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	53 Participants n=5 Participants
Region of Enrollment United States	53 participants n=5 Participants

PRIMARY outcome

Timeframe: 2 to 3 weeks

Population: Volunteers with evaluable data were included in the analysis.

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.

Outcome measures

Outcome measures
Measure	at Risk for Sleep Apnea n=48 Participants After approval from the Institutional Review Board and informed consent, we assessed cold and heat pain thresholds in volunteers after overnight polysomnography (PSG). We measured insulin growth factor binding protein-1 (IGFBP-1) a hypoxia-related serum marker. Pain tests were performed at baseline, placebo, and two effect site concentrations of remifentanil (1 and 2 mg/ml), an mu-opioid agonist. Linear mixed effects regression model was employed to evaluate the association of the lowest oxyhemoglobin saturation (SaO2) during sleep and IGFBP-1 with the changes in pain thresholds after remifentanil administration.
Experimental Cold-induced Pain - IGFBP-1	0.0025 [sec/(mcg/mL)] /pg/mL Interval 0.0009 to 0.0041

PRIMARY outcome

Timeframe: 2 to 3 weeks

Population: Volunteers with evaluable data were included in the analysis.

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.

Outcome measures

Outcome measures
Measure	at Risk for Sleep Apnea n=48 Participants After approval from the Institutional Review Board and informed consent, we assessed cold and heat pain thresholds in volunteers after overnight polysomnography (PSG). We measured insulin growth factor binding protein-1 (IGFBP-1) a hypoxia-related serum marker. Pain tests were performed at baseline, placebo, and two effect site concentrations of remifentanil (1 and 2 mg/ml), an mu-opioid agonist. Linear mixed effects regression model was employed to evaluate the association of the lowest oxyhemoglobin saturation (SaO2) during sleep and IGFBP-1 with the changes in pain thresholds after remifentanil administration.
Experimental Heat-induced Pain - IGFBP-1	-0.0001 ['C/(mcg/mL)] /pg/mL Interval -0.0001 to -0.0001

PRIMARY outcome

Timeframe: 2 to 3 weeks

Population: Volunteers with evaluable data were included in the analysis.

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.

Outcome measures

Outcome measures
Measure	at Risk for Sleep Apnea n=48 Participants After approval from the Institutional Review Board and informed consent, we assessed cold and heat pain thresholds in volunteers after overnight polysomnography (PSG). We measured insulin growth factor binding protein-1 (IGFBP-1) a hypoxia-related serum marker. Pain tests were performed at baseline, placebo, and two effect site concentrations of remifentanil (1 and 2 mg/ml), an mu-opioid agonist. Linear mixed effects regression model was employed to evaluate the association of the lowest oxyhemoglobin saturation (SaO2) during sleep and IGFBP-1 with the changes in pain thresholds after remifentanil administration.
Experimental Cold-induced Pain - SaO2	-0.9694 [sec/(mcg/mL)] /% Interval -1.9127 to -0.0261

PRIMARY outcome

Timeframe: 2 to 3 weeks

Population: Volunteers with evaluable data were included in the analysis.

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.

Outcome measures

Outcome measures
Measure	at Risk for Sleep Apnea n=48 Participants After approval from the Institutional Review Board and informed consent, we assessed cold and heat pain thresholds in volunteers after overnight polysomnography (PSG). We measured insulin growth factor binding protein-1 (IGFBP-1) a hypoxia-related serum marker. Pain tests were performed at baseline, placebo, and two effect site concentrations of remifentanil (1 and 2 mg/ml), an mu-opioid agonist. Linear mixed effects regression model was employed to evaluate the association of the lowest oxyhemoglobin saturation (SaO2) during sleep and IGFBP-1 with the changes in pain thresholds after remifentanil administration.
Experimental Heat-induced Pain - SaO2	-0.0172 ['C/(mcg/mL)] /% Interval -0.018 to 0.0556

Adverse Events

at Risk for Sleep Apnea

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Anthony Doufas, MD, PhD

Stanford University

Phone: (650) 498-7699

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place