- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00672438
Heritability of Opioid Effects: A Twin Study
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
The principal hypothesis to be evaluated is that the degree of analgesia provided by opioids in humans displays substantial familial aggregation, and is, in fact, heritable. These studies will use a classical twin paradigm to determine the role of genetics and the environment in influencing analgesia and a range of other opioid effects.
Specific Aims: (1) Determine the degree to which opioid analgesic responses show familial aggregation and make preliminary estimates of heritability using both a heat and cold pressor pain model, and (2) determine the degree to which non-analgesic opioid responses show familial aggregation and make preliminary estimates of heritability. Side effects such as sedation, nausea, respiratory depression, and pruritus, as well as the positive affective response, a measure of abuse potential, will be monitored. Monozygotic (MZ) and dizygotic (DZ) twin pairs (125 total pairs) will be tested under controlled pain laboratory conditions for their responses to opioid infusion using the complementary pain models while monitoring side effects and additional psychometric indices of mood, sleep, and abuse potential. The selected models provide unique mechanistic information because they involve different peripheral and/or central pain pathways. DNA samples will be collected for zygosity testing and banked for future studies.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
California
-
Stanford, California, United States, 94305
- Stanford University School of Medicine
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:Monozygotic or dizygotic twins ages 18-70
Exclusion Criteria:(1) Clinically relevant systemic diseases such as psychiatric, neurological, and dermatological conditions interfering with the collection and interpretation of study data (2) History of addiction (3) Allergy to study medication (4) Chronic intake of medication potentially interfering with pain processing (except oral contraceptives) (5) Intake of over-the-counter analgesics within the two days prior to study (6) Reynaud's disease (7) Pregnancy (8) Participation in other study within last 30 days (9) Personnel with direct access to addicting drugs
Study Plan
How is the study designed?
Design Details
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: Saline placebo infusion
Subjects will receive an intravenous infusion of normal saline.
|
Intravenous infusion of normal saline
|
Experimental: Alfentanil infusion
Subjects will receive an intravenous infusion of alfentanil.
|
Target controlled intravenous infusion of alfentanil at a plasma concentration of 100ng/ml
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Heat Pain Threshold
Time Frame: Participants underwent the pain testing measures at training prior to study procedures, at baseline and during each of the infusions.
|
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. |
Participants underwent the pain testing measures at training prior to study procedures, at baseline and during each of the infusions.
|
Cold Pain Threshold
Time Frame: Participants underwent the pain testing measures at training prior to study procedures, at baseline and during each of the infusions.
|
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. |
Participants underwent the pain testing measures at training prior to study procedures, at baseline and during each of the infusions.
|
Cold Pain Tolerance
Time Frame: Participants underwent the pain testing measures at training prior to study procedures, at baseline and during each of the infusions.
|
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. |
Participants underwent the pain testing measures at training prior to study procedures, at baseline and during each of the infusions.
|
Respiratory Rate
Time Frame: Measured throughout the study session ~ 5 hours
|
Breaths per minute counted by direct observation and additionally recorded / external electronic monitoring.
|
Measured throughout the study session ~ 5 hours
|
Transcutaneous Partial Pressure of Carbon Dioxide
Time Frame: Measured continuously throughout the study session ~ 5 hours
|
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.
|
Measured continuously throughout the study session ~ 5 hours
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Sedation
Time Frame: The trail making test was performed at training prior to study procedures, at baseline, and during each of the infusions.
|
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.
|
The trail making test was performed at training prior to study procedures, at baseline, and during each of the infusions.
|
Average Nausea
Time Frame: At the end of each infusion stage. 2 times total.
|
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.
|
At the end of each infusion stage. 2 times total.
|
Maximum Nausea
Time Frame: At the end of each infusion stage. 2 times total.
|
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.
|
At the end of each infusion stage. 2 times total.
|
Average Pruritis
Time Frame: At the end of each infusion stage. 2 times total.
|
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.
|
At the end of each infusion stage. 2 times total.
|
Maximum Pruritis
Time Frame: At the end of each infusion stage. 2 times total.
|
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.
|
At the end of each infusion stage. 2 times total.
|
Average Drug Liking
Time Frame: At the end of each infusion stage. 2 times total.
|
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.
|
At the end of each infusion stage. 2 times total.
|
Maximum Drug Liking
Time Frame: At the end of each infusion stage. 2 times total.
|
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.
|
At the end of each infusion stage. 2 times total.
|
Maximum Drug Disliking
Time Frame: At the end of each infusion stage. 2 times total.
|
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.
|
At the end of each infusion stage. 2 times total.
|
Sedation by Patient Report
Time Frame: At the end of each infusion stage. 2 times total.
|
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.
|
At the end of each infusion stage. 2 times total.
|
Collaborators and Investigators
Sponsor
Collaborators
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- SU-04212008-1119
- 13018 (Other Identifier: IRB Stanford University School of Medicine)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Pain
-
University Hospital Schleswig-HolsteinZealand University Hospital; European Regional Development Fund; Design School...CompletedPain, Acute | Pain, Chronic | Pain Measurement | Pain, CancerGermany
-
Flowonix MedicalApproved for marketingBack Pain | Leg Pain | Trunk Pain | Intractable Pain | Arm Pain
-
Dow University of Health SciencesRecruitingLow Back Pain | Chronic Low-back Pain | Low Back Pain, Mechanical | Mechanical Low Back Pain | Pain, Chronic | Pain, Back | Lower Back Pain Chronic | CLBP - Chronic Low Back PainPakistan
-
Dr. Negrin University HospitalCompletedPostoperative Pain, Acute | Postoperative Pain, ChronicSpain
-
George Washington UniversityRecruitingCervical Fusion | Pain, Back | Pain, Neck | Myofacial PainUnited States
-
Universitat Jaume ICompletedPain, Acute | Pain, Chronic | OncologySpain
-
Atatürk Chest Diseases and Chest Surgery Training...RecruitingPostoperative Pain | Postoperative Pain, Acute | Postoperative Pain, Chronic | VATSTurkey
-
Janssen Research & Development, LLCCompletedPain, Radiating | Pain, Burning | Pain, Crushing | Pain, Migratory | Pain, SplittingUnited States, France, Spain, Poland, Portugal
-
Atatürk Chest Diseases and Chest Surgery Training...RecruitingPostoperative Pain | Thoracotomy | Postoperative Pain, Acute | Postoperative Pain, ChronicTurkey
-
susanne beckerSNSFCompletedLow Back Pain | Pain, Acute | Pain, ChronicSwitzerland
Clinical Trials on Saline placebo infusion
-
The University of Texas Health Science Center,...National Institute of Neurological Disorders and Stroke (NINDS)CompletedTraumatic Brain InjuryUnited States
-
Novartis PharmaceuticalsCompletedSeasonal Allergic RhinitisUnited Kingdom
-
Xijing HospitalUnknownMyocardial InfarctionChina
-
University of AarhusDanish Heart FoundationCompletedPulmonary Hypertension | KetonemiaDenmark
-
Bispebjerg HospitalPsychiatric Centre RigshospitaletCompletedCognitive Change | Type2 Diabetes | KetonemiaDenmark
-
Queen's UniversityWithdrawnRenal Failure | Contrast Nephropathy
-
Yale UniversityWithdrawnOvarian Hyperstimulation SyndromeUnited States
-
Assaf-Harofeh Medical CenterNot yet recruiting
-
University of CalgaryNot yet recruitingPostural Orthostatic Tachycardia Syndrome | Post Acute Sequelae of SARS CoV 2 Infection
-
University of California, San DiegoCompletedBreast Cancer | Mastectomy | Paravertebral Catheter InsertionUnited States