PainNCT00672438
Heritability of Opioid Effects: A Twin Study
A study testing Alfentanil in people with Pain, run by Martin Angst at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Pain
- What is being tested?
- Alfentanil
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 242 participants
- Where
- 1 siteUnited States
- Study dates
- May 2008to Jun 2010
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
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
Trial locations and contacts
1 site in 1 country.
United States1 site
Stanford University School of Medicine
Stanford, California, 94305
About this 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.
Read the 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
- Being tested
- Alfentanil, Saline placebo infusion
- Medical subject headings
- Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AlfentanilDrug
Also called Alfenta
Target controlled intravenous infusion of alfentanil at a plasma concentration of 100ng/ml
Saline placebo infusionOther
Intravenous infusion of normal saline
| Study group | Role | What they receive |
|---|---|---|
| Saline placebo infusion | Placebo comparator | Subjects will receive an intravenous infusion of normal saline. Receives: Other: Saline placebo infusion |
| Alfentanil infusion | Experimental | Subjects will receive an intravenous infusion of alfentanil. Receives: Drug: Alfentanil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Heat Pain Threshold
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.
Measured: Participants underwent the pain testing measures at training prior to study procedures, at baseline and during each of the infusions.
Cold Pain Threshold
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.
Measured: Participants underwent the pain testing measures at training prior to study procedures, at baseline and during each of the infusions.
Cold Pain Tolerance
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.
Measured: Participants underwent the pain testing measures at training prior to study procedures, at baseline and during each of the infusions.
Respiratory Rate
Breaths per minute counted by direct observation and additionally recorded / external electronic monitoring.
Measured: Measured throughout the study session ~ 5 hours
Transcutaneous Partial Pressure of Carbon Dioxide
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: Measured continuously throughout the study session ~ 5 hours
Secondary outcomes (9)
Sedation
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.
Measured: The trail making test was performed at training prior to study procedures, at baseline, and during each of the infusions.
Average Nausea
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.
Measured: At the end of each infusion stage. 2 times total.
Maximum Nausea
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.
Measured: At the end of each infusion stage. 2 times total.
Average Pruritis
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.
Measured: At the end of each infusion stage. 2 times total.
Maximum Pruritis
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.
Measured: At the end of each infusion stage. 2 times total.
Average Drug Liking
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.
Measured: At the end of each infusion stage. 2 times total.
Maximum Drug Liking
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.
Measured: At the end of each infusion stage. 2 times total.
Maximum Drug Disliking
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.
Measured: At the end of each infusion stage. 2 times total.
Sedation by Patient Report
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.
Measured: At the end of each infusion stage. 2 times total.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2008 (estimated)
- Study startMay 2008
- Primary completionJun 2010
- Study completionJun 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for PainStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 242 participants (actual)
Sponsor and investigators
- Lead sponsor
- Martin Angst
- Sponsor type
- University, hospital or other
- Collaborators
- SRI International
- Responsible party
- Sponsor-investigator, Martin Angst, Stanford University
- Investigators
- Martin S Angst, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00672438
- Sponsor's protocol ID
- SU-04212008-1119
- Other IDs
- 13018
- Status last verified
- Jan 2017
- First submitted
- 2 May 2008
- Last updated
- 6 Jan 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Heritability of Opioid Effects: A Twin Study
- ClinicalTrials.gov ID
- NCT00672438
- Acronym / sponsor ID
- SU-04212008-1119
- Conditions
- Pain
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 242 participants (actual)
- Lead sponsor
- Martin AngstUniversity, hospital or other
- Collaborators
- SRI International
- Study start
- May 2008
- Primary completion
- Jun 2010 (actual)
- Study completion
- Jun 2010 (actual)
- First posted
- 6 May 2008 (estimated)
- Results
- Posted 21 Jul 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Saline placebo infusion | Placebo comparator | Other: Saline placebo infusionSubjects will receive an intravenous infusion of normal saline. |
| Alfentanil infusion | Experimental | Drug: AlfentanilSubjects will receive an intravenous infusion of alfentanil. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AlfentanilAlso: AlfentaTarget controlled intravenous infusion of alfentanil at a plasma concentration of 100ng/ml | Drug | Alfentanil infusion |
| Saline placebo infusionIntravenous infusion of normal saline | Other | Saline placebo infusion |
Primary outcome
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.
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.
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.
Respiratory Rate
Time frame: Measured throughout the study session ~ 5 hours
Breaths per minute counted by direct observation and additionally recorded / external electronic monitoring.
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.
9 secondary outcomes
Sedation
Time frame: 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.
Maximum Nausea
Time frame: At the end of each infusion stage. 2 times total.
Average Pruritis
Time frame: At the end of each infusion stage. 2 times total.
Maximum Pruritis
Time frame: 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.
Maximum Drug Liking
Time frame: 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.
Sedation by Patient Report
Time frame: At the end of each infusion stage. 2 times total.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jan 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Martin S Angst principal investigator
Stanford University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Alfentanil in people with Pain, run by Martin Angst at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Jan 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Jul 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jan 2017.