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Completed

NCT Number: NCT00672438

Heritability of Opioid Effects: A Twin Study

Proposed twin study will test to what degree inter-individual differences in pain sensitivity and amount of pain relief in response to opioid therapy are inherited or alternatively, are due to environmental factors. This knowledge is important to guide future studies trying to explain such inter-individual differences. For example, finding that differences are largely due to environmental factors would discourage genomic studies and emphasize epidemiological studies.

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Key information

Conditions

Pain Neurologic Manifestations Pathological Conditions, Signs and Symptoms Signs and Symptoms

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Stanford University School of Medicine

Stanford, California, 94305, United States

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

alfentanil

Drug

Target controlled intravenous infusion of alfentanil at a plasma concentration of 100ng/ml

Other names: Alfenta

Saline placebo infusion

Other

Intravenous infusion of normal saline

Primary outcomes

  1. 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.

  2. 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.

  3. 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.

  4. Respiratory Rate

    Time frame: Measured throughout the study session ~ 5 hours

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

  5. 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.

Secondary outcomes

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

Sponsors and collaborators

Lead sponsor

Martin Angst

Other

Collaborators

  • SRI International

Registry information

Important dates

Study start
2008
Primary completion
2010
Study completion
2010
First posted
May 6, 2008
Registry last updated
Jan 6, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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