Clinical trial NCT00672438: Heritability of Opioid Effects: A Twin Study
Official title: Heritability of Opioid Effects: A Twin Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Pain
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: SRI International
First posted: 2008-05-06
Enrollment: 242
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER

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.

Eligibility 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

Primary outcomes:
measure: Heat Pain Threshold
timeFrame: Participants underwent the pain testing measures at training prior to study procedures, at baseline and during each of the infusions.
measure: Cold Pain Threshold
timeFrame: Participants underwent the pain testing measures at training prior to study procedures, at baseline and during each of the infusions.
measure: Cold Pain Tolerance
timeFrame: Participants underwent the pain testing measures at training prior to study procedures, at baseline and during each of the infusions.
measure: Respiratory Rate
timeFrame: Measured throughout the study session ~ 5 hours
measure: Transcutaneous Partial Pressure of Carbon Dioxide
timeFrame: Measured continuously throughout the study session ~ 5 hours
Secondary outcomes:
measure: Sedation
timeFrame: The trail making test was performed at training prior to study procedures, at baseline, and during each of the infusions.
measure: Average Nausea
timeFrame: At the end of each infusion stage. 2 times total.
measure: Maximum Nausea
timeFrame: At the end of each infusion stage. 2 times total.
measure: Average Pruritis
timeFrame: At the end of each infusion stage. 2 times total.
measure: Maximum Pruritis
timeFrame: At the end of each infusion stage. 2 times total.
measure: Average Drug Liking
timeFrame: At the end of each infusion stage. 2 times total.
measure: Maximum Drug Liking
timeFrame: At the end of each infusion stage. 2 times total.
measure: Maximum Drug Disliking
timeFrame: At the end of each infusion stage. 2 times total.
measure: Sedation by Patient Report
timeFrame: At the end of each infusion stage. 2 times total.
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
Study officials:
affiliation: Stanford University
name: Martin S Angst
role: PRINCIPAL_INVESTIGATOR
References: