Heritability of Opioid Effects: A Twin Study

NCT ID: NCT00672438

Last Updated: 2017-01-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 242 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-05-31
• Study Completion Date: 2010-06-30

Brief Summary

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.

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.

Conditions

Pain

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Blinding Strategy: DOUBLE

Study Groups

Saline placebo infusion

Subjects will receive an intravenous infusion of normal saline.

Group Type: PLACEBO_COMPARATOR

Saline placebo infusion

Intervention Type: OTHER

Intravenous infusion of normal saline

Alfentanil infusion

Subjects will receive an intravenous infusion of alfentanil.

Group Type: EXPERIMENTAL

Alfentanil

Intervention Type: DRUG

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

Interventions

Alfentanil

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

Intervention Type: DRUG

Saline placebo infusion

Intravenous infusion of normal saline

Intervention Type: OTHER

Other Intervention Names

Alfenta

Eligibility Criteria

Inclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

SRI International

INDUSTRY

Sponsor Role: collaborator

Martin Angst

OTHER

Sponsor Role: lead

Responsible Party

Martin Angst

Professor of Anesthesia

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Martin S Angst

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

Stanford University School of Medicine

Stanford, California, United States

Countries

United States

Other Identifiers

13018

Identifier Type: OTHER

Identifier Source: secondary_id

SU-04212008-1119

Identifier Type: -

Identifier Source: org_study_id