Trial Outcomes & Findings for Heritability of Opioid Effects: A Twin Study (NCT NCT00672438)

NCT ID: NCT00672438

Last Updated: 2017-01-06

Results Overview

Degrees Centigrade Heat pain was induced with a thermal sensory analyzer (TSA-II, Medoc Advanced Medical Systems, Durham, North Carolina). A thermode was placed in contact with skin at the volar forearm. Starting at a comfortable temperature, the thermode temperature was increased at a measured rate. Study participants pushed a button of a hand-held device at the onset of pain at which point the thermode immediately reduced the temperature.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 242 participants
• Primary outcome timeframe: Participants underwent the pain testing measures at training prior to study procedures, at baseline and during each of the infusions.
• Results posted on: 2017-01-06

Participant Flow

Twins were recruited by a joint effort of SRI International and Stanford University School of Medicine. Initial contact and primary enrollment was the responsibility of study staff of SRI International. Recruitment was mainly achieved through the Twin Research Registry and advertisements broadcasted by regional radio stations

Participants were required to fast overnight except for clear liquids that were allowed up to 2 hours before starting the drug infusion. Subjects were also required to have at least 6 hours of night-time sleep before a study session. Some participants withdrew prior to study participation.

Participant milestones

Measure	Alfentanil Infusion Prior to Saline Placebo Infusion 50% of participants were randomized to receive an infusion of alfentanil via a computer-controlled infusion targeting steady-state plasma concentration of 100ng/ml prior to a saline placebo infusion. All other procedures were identical in both groups.	Saline Placebo Infusion Prior to Alfentanil Infusion 50% of participants were randomized to receive a saline placebo infusion prior to an infusion of alfentanil via a computer-controlled infusion pump targeting a steady-state plasma concentration of 100ng/ml. All other procedures were identical in both groups.
Infusion 1 STARTED	119	118
Infusion 1 COMPLETED	119	118
Infusion 1 NOT COMPLETED	0	0
Washout STARTED	119	118
Washout COMPLETED	119	118
Washout NOT COMPLETED	0	0
Infusion 2 STARTED	119	118
Infusion 2 COMPLETED	119	118
Infusion 2 NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Heritability of Opioid Effects: A Twin Study

Baseline characteristics by cohort

Measure	Alfentanil Infusion Prior to Saline Placebo Infusion n=122 Participants 50% of participants were randomized to receive an infusion of alfentanil prior to a saline placebo infusion. All other procedures were identical in both groups.	Saline Placebo Infusion Prior to Alfentanil Infusion n=120 Participants 50% of participants were randomized to receive a saline placebo infusion prior to an infusion of alfentanil. All other procedures were identical in both groups.	Total n=242 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	122 Participants n=5 Participants	120 Participants n=7 Participants	242 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Gender Female	76 Participants n=5 Participants	74 Participants n=7 Participants	150 Participants n=5 Participants
Gender Male	46 Participants n=5 Participants	46 Participants n=7 Participants	92 Participants n=5 Participants
Region of Enrollment United States	122 participants n=5 Participants	120 participants n=7 Participants	242 participants n=5 Participants

PRIMARY outcome

Timeframe: Participants underwent the pain testing measures at training prior to study procedures, at baseline and during each of the infusions.

Population: All participants were included for analysis.

Degrees Centigrade

Heat pain was induced with a thermal sensory analyzer (TSA-II, Medoc Advanced Medical Systems, Durham, North Carolina). A thermode was placed in contact with skin at the volar forearm. Starting at a comfortable temperature, the thermode temperature was increased at a measured rate. Study participants pushed a button of a hand-held device at the onset of pain at which point the thermode immediately reduced the temperature.

Outcome measures

Measure	Alfentanil Infusion n=228 Participants A controlled intravenous infusion was run at a rate to target an alfentanil plasma concentration of 100ng/ml	Saline Infusion n=228 Participants All participants received NS at an infusion rate identical to the alfentanil rate.
Heat Pain Threshold	49.6 degrees centigrade Interval 48.3 to 50.4	48.6 degrees centigrade Interval 47.1 to 49.3

PRIMARY outcome

Timeframe: Participants underwent the pain testing measures at training prior to study procedures, at baseline and during each of the infusions.

Population: All participants were included for analysis.

Time in seconds

Sensitivity to cold-pressor pain was tested by asking subjects to immerse their hand up to the wrist in ice water (1-2 C) continuously re-circulated within a 12-L container with the palm of the hand in full contact with the bottom of the container.They were asked to indicate the onset of pain - reported as pain threshold.

Outcome measures

Measure	Alfentanil Infusion n=228 Participants A controlled intravenous infusion was run at a rate to target an alfentanil plasma concentration of 100ng/ml	Saline Infusion n=228 Participants All participants received NS at an infusion rate identical to the alfentanil rate.
Cold Pain Threshold	15 Seconds Interval 9.0 to 25.0	8 Seconds Interval 6.0 to 13.0

PRIMARY outcome

Timeframe: Participants underwent the pain testing measures at training prior to study procedures, at baseline and during each of the infusions.

Population: All participants were included for analysis.

Time in seconds

Sensitivity to cold-pressor pain was tested by asking subjects to immerse their hand up to the wrist in ice water (1-2 C) continuously re-circulated within a 12-L container with the palm of the hand in full contact with the bottom of the container.They were asked to remove their hand from the water bath when it was no longer tolerable - reported as pain tolerance.

Outcome measures

Measure	Alfentanil Infusion n=228 Participants A controlled intravenous infusion was run at a rate to target an alfentanil plasma concentration of 100ng/ml	Saline Infusion n=228 Participants All participants received NS at an infusion rate identical to the alfentanil rate.
Cold Pain Tolerance	32 Seconds Interval 20.0 to 55.0	17 Seconds Interval 11.0 to 26.0

PRIMARY outcome

Timeframe: Measured throughout the study session ~ 5 hours

Population: All participants were included for analysis.

Breaths per minute counted by direct observation and additionally recorded / external electronic monitoring.

Outcome measures

Measure	Alfentanil Infusion n=228 Participants A controlled intravenous infusion was run at a rate to target an alfentanil plasma concentration of 100ng/ml	Saline Infusion n=228 Participants All participants received NS at an infusion rate identical to the alfentanil rate.
Respiratory Rate	11 Breaths per minute Interval 9.0 to 13.0	14 Breaths per minute Interval 12.0 to 16.0

PRIMARY outcome

Timeframe: Measured continuously throughout the study session ~ 5 hours

Population: All participants were included for analysis.

Partial pressure of transcutaneous carbon dioxide (CO2) was measured with aid of a pO2/pCO2-electrode (Perimed Inc., North Royalton, OH) mounted to the anterior chest wall.

Outcome measures

Measure	Alfentanil Infusion n=228 Participants A controlled intravenous infusion was run at a rate to target an alfentanil plasma concentration of 100ng/ml	Saline Infusion n=228 Participants All participants received NS at an infusion rate identical to the alfentanil rate.
Transcutaneous Partial Pressure of Carbon Dioxide	47.7 mmHg Interval 43.4 to 52.0	40.3 mmHg Interval 37.6 to 42.9

SECONDARY outcome

Timeframe: The trail making test was performed at training prior to study procedures, at baseline, and during each of the infusions.

Population: All participants were included for analysis.

Sedative opioid effects were assessed with the trail-making test (TMT) (Angst et al., 2004; Oswald and Roth, 1987). The TMT is a paper-and pencil test consisting of 4 different matrices listing numbers 1-90 in a 9 × 10 format. Subsequent numbers are located in neighboring rows or columns. Matrices were allocated randomly. Subjects had to connect numbers 1-90 as quickly as possible and the time to completion was recorded.

Outcome measures

Measure	Alfentanil Infusion n=228 Participants A controlled intravenous infusion was run at a rate to target an alfentanil plasma concentration of 100ng/ml	Saline Infusion n=228 Participants All participants received NS at an infusion rate identical to the alfentanil rate.
Sedation	70 Time in seconds Interval 59.0 to 87.0	63 Time in seconds Interval 56.0 to 75.0

SECONDARY outcome

Timeframe: At the end of each infusion stage. 2 times total.

Population: All participants were included for analysis.

At the end of an infusion stage participants were asked to rate the average severity of nausea on a 100-mm visual analog scale (VAS) anchored by the words "not at all" and "as much as possible." This means that the scale is 100mm long where one extreme end of the scale represents "0", and 0 represents no nausea experienced. The other extreme end of the scale represents "100", and 100 represents as much nausea as possible. Participants are asked to indicate what point on that continuum best represents their average experience.

Outcome measures

Measure	Alfentanil Infusion n=228 Participants A controlled intravenous infusion was run at a rate to target an alfentanil plasma concentration of 100ng/ml	Saline Infusion n=228 Participants All participants received NS at an infusion rate identical to the alfentanil rate.
Average Nausea	1 numerical score Interval 0.0 to 32.0	0 numerical score Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: At the end of each infusion stage. 2 times total.

Population: All participants were included for analysis.

At the end of an infusion stage participants were asked to rate the maximum severity of nausea on a 100-mm visual analog scale (VAS) anchored by the words "not at all" and "as much as possible." This means that the scale is 100mm long where one extreme end of the scale represents "0", and 0 represents no nausea experienced. The other extreme end of the scale represents "100", and 100 represents as much nausea as possible. Participants are asked to indicate what point on that continuum best represents their maximum experience of nausea.

Outcome measures

Measure	Alfentanil Infusion n=228 Participants A controlled intravenous infusion was run at a rate to target an alfentanil plasma concentration of 100ng/ml	Saline Infusion n=228 Participants All participants received NS at an infusion rate identical to the alfentanil rate.
Maximum Nausea	8 numerical score Interval 0.0 to 70.0	0 numerical score Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: At the end of each infusion stage. 2 times total.

Population: All participants were included for analysis.

At the end of an infusion stage participants were asked to rate the average severity of pruritis on a 100-mm visual analog scale (VAS) anchored by the words "not at all" and "as much as possible." This means that the scale is 100mm long where one extreme end of the scale represents "0", and 0 represents no pruritis experienced. The other extreme end of the scale represents "100", and 100 represents as much pruritis as possible. Participants are asked to indicate what point on that continuum best represents their average experience of pruritis.

Outcome measures

Measure	Alfentanil Infusion n=228 Participants A controlled intravenous infusion was run at a rate to target an alfentanil plasma concentration of 100ng/ml	Saline Infusion n=228 Participants All participants received NS at an infusion rate identical to the alfentanil rate.
Average Pruritis	20 numerical score Interval 0.0 to 45.0	0 numerical score Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: At the end of each infusion stage. 2 times total.

Population: All participants were included for analysis.

At the end of an infusion stage participants were asked to rate the maximum severity of pruritis on a 100-mm visual analog scale (VAS) anchored by the words "not at all" and "as much as possible." This means that the scale is 100mm long where one extreme end of the scale represents "0", and 0 represents no pruritis experienced. The other extreme end of the scale represents "100", and 100 represents as much pruritis as possible. Participants are asked to indicate what point on that continuum best represents their maximun experience of pruritis.

Outcome measures

Measure	Alfentanil Infusion n=228 Participants A controlled intravenous infusion was run at a rate to target an alfentanil plasma concentration of 100ng/ml	Saline Infusion n=228 Participants All participants received NS at an infusion rate identical to the alfentanil rate.
Maximum Pruritis	35 numerical score Interval 0.0 to 65.0	0 numerical score Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: At the end of each infusion stage. 2 times total.

Population: All participants were included for analysis.

At the end of an infusion stage participants were asked, "How much did you like the drug on average (100-mm VAS, 0 _ "not at all," 100 _ "as much as possible")? The VAS scale is 100mm long where one extreme end of the scale represents "0", and 0 indicates the participant did not like the drug experience. The other extreme end of the scale represents "100", and 100 indicates that the participant liked the drug experience as much as possible. Participants are asked to indicate what point on that continuum best represents the their experience.

Outcome measures

Measure	Alfentanil Infusion n=228 Participants A controlled intravenous infusion was run at a rate to target an alfentanil plasma concentration of 100ng/ml	Saline Infusion n=228 Participants All participants received NS at an infusion rate identical to the alfentanil rate.
Average Drug Liking	50 numerical score Interval 0.0 to 75.0	0 numerical score Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: At the end of each infusion stage. 2 times total.

Population: All participants were included for analysis.

At the end of an infusion stage participants were asked, "What was the maximum that you liked the drug at any moment (VAS)? (100-mm VAS, 0 _ "not at all," 100 _ "as much as possible")? The VAS scale is 100mm long where one extreme end of the scale represents "0", and 0 indicates the participant did not like the drug experience. The other extreme end of the scale represents "100", and 100 indicates that the participant liked the drug experience as much as possible. Participants are asked to indicate what point on that continuum best represents the their experience.

Outcome measures

Measure	Alfentanil Infusion n=228 Participants A controlled intravenous infusion was run at a rate to target an alfentanil plasma concentration of 100ng/ml	Saline Infusion n=228 Participants All participants received NS at an infusion rate identical to the alfentanil rate.
Maximum Drug Liking	75 numerical score Interval 40.0 to 90.0	0 numerical score Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: At the end of each infusion stage. 2 times total.

Population: All participants were included for analysis.

At the end of an infusion stage participants were asked, "What was the maximum that you disliked the drug at any moment (VAS)? (100-mm VAS, 0 _ "not at all," 100 _ "as much as possible")? The VAS scale is 100mm long where one extreme end of the scale represents "0", and 0 indicates the participant did not like the drug experience. The other extreme end of the scale represents "100", and 100 indicates that the participant liked the drug experience as much as possible. Participants are asked to indicate what point on that continuum best represents the most they disliked the drug experience.

Outcome measures

Measure	Alfentanil Infusion n=228 Participants A controlled intravenous infusion was run at a rate to target an alfentanil plasma concentration of 100ng/ml	Saline Infusion n=228 Participants All participants received NS at an infusion rate identical to the alfentanil rate.
Maximum Drug Disliking	23 numerical score Interval 0.0 to 70.0	0 numerical score Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: At the end of each infusion stage. 2 times total.

Population: All participants were included for analysis.

Sedation was assessed by measuring cognitive speed and by asking participants to indicate on a 100-mm visual analog scale (VAS) how sedated they felt. This means that the scale is 100mm long where one extreme end of the scale represents "0", and 0 represents no sedation was experienced. The other extreme end of the scale represents "100", and 100 represents as much sedation as possible. Participants are asked to indicate what point on that continuum best represents their experience of sedation.

Outcome measures

Measure	Alfentanil Infusion n=228 Participants A controlled intravenous infusion was run at a rate to target an alfentanil plasma concentration of 100ng/ml	Saline Infusion n=228 Participants All participants received NS at an infusion rate identical to the alfentanil rate.
Sedation by Patient Report	75 numerical score Interval 60.0 to 87.0	0 numerical score Interval 0.0 to 15.0

Adverse Events

Alfentanil

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

Dr. Martin Angst, Professor of Anesthesia

Stanford University

Phone: 650-498-5109

Email: ang@stanford.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place