Placebo AnalgesiaNCT01328561
Oxytocin and Arginine Vasopressin in Pain Relief
An observational study of Placebo Analgesia, run by National Institute of Mental Health (NIMH) at 1 site in United States.
Trial summary
Background: Oxytocin, a substance produced mostly in the brain, plays a role in influencing social interactions and reactions to stress, and may be related to pain. Arginine vasopressin, a hormone that regulates water, sugar, and salt in the blood, influences hostile behaviors and reactions to stress, and may also be… Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Placebo Analgesia
- How many people
- 167 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Mar 2011to 4 Mar 2015
- Phase
- Observational
- Are there results?
- None posted in the registry
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 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Men and Women
- Aged between 18-55 years
- Able to understand and speak the English language
Who cannot join
- Any significant medical or neurological problems (e.g. cardiovascular illness, respiratory illness, neurologic illness, seizures, etc.)
- History of angioedema
- High blood pressure (above 140 mmHg) or symptomatic low blood pressure
- History of fainting
- A family history of mania, schizophrenia, or other psychoses (first-degree relatives only)
- A history of mania, schizophrenia, or other psychoses
Show all 26Show fewer
- Any current Axis I psychiatric disorders (e.g. depression and anxiety)
- Lifetime alcohol/drug dependence
- Alcohol/drug abuse in the past year
- Current use of psychotropic medication
- Impaired hearing
- Pregnancy
- Breast-feeding
- Smokers (use of any form of nicotine during the last six months)
- Color-blindness (e.g. difficulty to distinguish between red and green colors)
- History of fainting and symptomatic hypotension will be reviewed by the clinicians responsible for the screening and study on a case-by-case basis.
- ADDITIONAL EXCLUSION CRITERIA FOR THE MRI AND MEG STUDIES
- Participants taking part in the MRI (Experiment 2) and MEG (Experiment 3) studies will also be excluded in case of:
- Metal slivers or shavings lodged in the tissues of the head or neck
- Surgical clips or shrapnel in or near the brain or blood vessels
- Any metallic objects in the eyes or central nervous system, and any form of implant wire or metal device that may concentrate radiofrequency fields
- Head trauma with loss of consciousness in the last year or any evidence of functional impairment due to and persisting after head trauma.
- Previously worked in metal fields or machines that may have left any metallic fragments in or near your eyes.
- Tattooed makeup (eyeliner, lip, etc) or general tattoos in a dangerous location on your body.
- Any non-organic implant or any other device such as: cardiac pacemaker, insulin infusion pump, implanted drug infusion device, cochlear, otologic, or ear implant, transdermal medication patch (Nitro), any metallic implants or objects, body piercing(s), bone/joint pin, screw, nail, plate, wire sutures or surgical staples, or shunt.
- Any psychological contraindications for MRI (e.g., fear of closed places).
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: The Role of Oxytocin and Arginine Vasopressin in Human Placebo Analgesia
Background:
- Oxytocin, a substance produced mostly in the brain, plays a role in influencing social interactions and reactions to stress, and may be related to pain. Arginine vasopressin, a hormone that regulates water, sugar, and salt in the blood, influences hostile behaviors and reactions to stress, and may also be related to pain. Researchers are interested in investigating both substances and their relationship to pain in healthy volunteers.
Read more
Objectives:
- To evaluate the effects of oxytocin and arginine vasopressin on pain in healthy volunteers.
Eligibility:
- Healthy volunteers between 18 and 55 years of age.
Design:
- This study involves two 2-hour testing sessions held 1 day apart. Each session includes the administration of oxytocin, arginine vasopressin, or placebo (a nonactive substance), or no drug. The drugs and the placebo will be given by a nasal spray.
- At the first visit, participants will provide blood and saliva samples to measure hormone levels, and will be asked to fill out questionnaires about some psychological factors such as anxiety and empathy. Participants will then have an assessment of their sensitivity to pain, consisting of a brief electrical stimulation that lasts less than 1 second. After the pain assessment, participants will receive oxytocin, arginine vasopressin, placebo, or no drug at all, and will be monitored to provide baseline information. Participants will then have another pain sensitivity test and will complete the questionnaires again, and provide another saliva sample.
- At the second visit, participants will provide another saliva sample; receive oxytocin, arginine vasopressin, placebo, or no drug at all; and have tests of pain sensitivity and a pain-relieving procedure. During the pain-relieving procedure, participants will receive brief, moderately painful electrical shocks on the back of the nondominant hand and a low-level electrical stimulation on the middle finger that counteracts or reduces the pain from the shocks. Participants will rate their pain perception at the end of each stimulation by using a visual scale ranging from 0 (no pain) to 10 (maximum imaginable pain). The experiment ends with a final saliva collection and completion of the psychological questionnaires.
Read the detailed description
Objective:
It is well known that social and contextual cues and the whole atmosphere around the patient, such as words, attitudes, and providers behaviors, all contribute to evoke placebo responses. Moreover, an extensive literature investigating prosocial behaviors (e.g. ability to share another s feelings, imitation, mimicry) suggests that social modeling is critical in developing learning processes across species, including social influences on psychophysical aspects of pain. Only recently, it has been demonstrated that observing the beneficial effects in a demonstrator induces substantial placebo analgesic responses which are positively correlated with empathy. A crucial role in social behaviors is played by oxytocin (OXT) and arginine vasopressin (AVP), two neuropeptides, produced mostly in the hypothalamus and acting on certain brain regions whose function is associated with emotion perception (amygdale and nucleus accumbens), eye-gaze, trust and processing of positive and negative social cues. Since beliefs, trust and contextual cues are important elements of the clinicianpatient relationship and socially-induced placebo effects, it is reasonable to hypothesize that OXT and AVP may be one of the endogenous substances that trigger contextual and interpersonal placebo responses. By viewing interpersonal healing as a central causal process (or a set of related causal processes) within the domain of pain modulation, it is possible to probe the potential role for OXT and AVP in the modulation of a placebo response. In pursuit of this goal, we use a neuropharmacological intervention with OXT and AVP agonists in combination with a behavioral, brain imaging and genetic approach.
Study population:
Healthy men and women participants aging from 18 to 55 years.
Design:
We will investigate the role of oxytocinergic system in the processing of social cues by using a model of pain and interpersonal placebo analgesia already tested (9). The following drugs will be used: 1) oxytocin, 2) arginine vasopressin, and 3) placebo.
Outcome measures:
Primary outcomes are subjective pain reports (Experiment 1) and brain- and cortical -related responses (Experiments 2 and 3). Secondary measures include skin conductance response, heart rate, cortisol, subjective measures of empathy; trait and state anxiety measures; and functional pain-related genetic polymorphisms.
- Conditions
- Placebo Analgesia
- Keywords
- Arginine, Oxytocin, Vasopressin, Placebo, Analgesia, Healthy Volunteer, HV
- Medical subject headings
- Diabetes Insipidus, Agnosia
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Apr 2011 (estimated)
- Study start17 Mar 2011
- Study completion4 Mar 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Placebo AnalgesiaStudies 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
- Observational
- Time perspective
- Prospective
- Enrolment
- 167 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute of Mental Health (NIMH)
- Sponsor type
- US National Institutes of Health
- Investigators
- Luana Colloca, M.D., Principal investigator, National Institute of Mental Health (NIMH)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01328561
- Sponsor's protocol ID
- 110104
- Other IDs
- 11-M-0104
- Status last verified
- 4 Mar 2015
- First submitted
- 1 Apr 2011
- Last updated
- 5 Jul 2018
- Results posted
- No
Publications
Colloca L, Benedetti F. Placebos and painkillers: is mind as real as matter? Nat Rev Neurosci. 2005 Jul;6(7):545-52. doi: 10.1038/nrn1705.
PubMed 15995725Colloca L, Benedetti F, Porro CA. Experimental designs and brain mapping approaches for studying the placebo analgesic effect. Eur J Appl Physiol. 2008 Mar;102(4):371-80. doi: 10.1007/s00421-007-0593-6. Epub 2007 Oct 25.
PubMed 17960416Zubieta JK, Stohler CS. Neurobiological mechanisms of placebo responses. Ann N Y Acad Sci. 2009 Mar;1156:198-210. doi: 10.1111/j.1749-6632.2009.04424.x.
PubMed 19338509Colloca L, Schenk LA, Nathan DE, Robinson OJ, Grillon C. When Expectancies Are Violated: A Functional Magnetic Resonance Imaging Study. Clin Pharmacol Ther. 2019 Dec;106(6):1246-1252. doi: 10.1002/cpt.1587. Epub 2019 Sep 10.
PubMed 31350784Colloca L, Grillon C. Understanding placebo and nocebo responses for pain management. Curr Pain Headache Rep. 2014 Jun;18(6):419. doi: 10.1007/s11916-014-0419-2.
PubMed 24771206
Study at a glance
From the registry record, last updated by the sponsor on 5 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Oxytocin and Arginine Vasopressin in Human Placebo Analgesia
- ClinicalTrials.gov ID
- NCT01328561
- Acronym / sponsor ID
- 110104
- Conditions
- Placebo Analgesia
- Keywords
- Arginine, Oxytocin, Vasopressin, Placebo, Analgesia, Healthy Volunteer, HV
- Study type
- Observational
- Recruitment status
- Terminated
- Enrolment
- 167 participants (actual)
- Lead sponsor
- National Institute of Mental Health (NIMH)US National Institutes of Health
- Study start
- 17 Mar 2011
- Study completion
- 4 Mar 2015
- First posted
- 4 Apr 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
- Oxytocin, a substance produced mostly in the brain, plays a role in influencing social interactions and reactions to stress, and may be related to pain. Arginine vasopressin, a hormone that regulates water, sugar, and salt in the blood, influences hostile behaviors and reactions to stress, and may also be related to pain. Researchers are interested in investigating both substances and their relationship to pain in healthy volunteers.
Objectives:
- To evaluate the effects of oxytocin and arginine vasopressin on pain in healthy volunteers.
Eligibility:
- Healthy volunteers between 18 and 55 years of age.
Design:
- This study involves two 2-hour testing sessions held 1 day apart. Each session includes the administration of oxytocin, arginine vasopressin, or placebo (a nonactive substance), or no drug. The drugs and the placebo will be given by a nasal spray.
- At the first visit, participants will provide blood and saliva samples to measure hormone levels, and will be asked to fill out questionnaires about some psychological factors such as anxiety and empathy. Participants will then have an assessment of their sensitivity to pain, consisting of a brief electrical stimulation that lasts less than 1 second. After the pain assessment, participants will receive oxytocin, arginine vasopressin, placebo, or no drug at all, and will be monitored to provide baseline information. Participants will then have another pain sensitivity test and will complete the questionnaires again, and provide another saliva sample.
- At the second visit, participants will provide another saliva sample; receive oxytocin, arginine vasopressin, placebo, or no drug at all; and have tests of pain sensitivity and a pain-relieving procedure. During the pain-relieving procedure, participants will receive brief, moderately painful electrical shocks on the back of the nondominant hand and a low-level electrical stimulation on the middle finger that counteracts or reduces the pain from the shocks. Participants will rate their pain perception at the end of each stimulation by using a visual scale ranging from 0 (no pain) to 10 (maximum imaginable pain). The experiment ends with a final saliva collection and completion of the psychological questionnaires.
Detailed description
Objective:
It is well known that social and contextual cues and the whole atmosphere around the patient, such as words, attitudes, and providers behaviors, all contribute to evoke placebo responses. Moreover, an extensive literature investigating prosocial behaviors (e.g. ability to share another s feelings, imitation, mimicry) suggests that social modeling is critical in developing learning processes across species, including social influences on psychophysical aspects of pain. Only recently, it has been demonstrated that observing the beneficial effects in a demonstrator induces substantial placebo analgesic responses which are positively correlated with empathy. A crucial role in social behaviors is played by oxytocin (OXT) and arginine vasopressin (AVP), two neuropeptides, produced mostly in the hypothalamus and acting on certain brain regions whose function is associated with emotion perception (amygdale and nucleus accumbens), eye-gaze, trust and processing of positive and negative social cues. Since beliefs, trust and contextual cues are important elements of the clinicianpatient relationship and socially-induced placebo effects, it is reasonable to hypothesize that OXT and AVP may be one of the endogenous substances that trigger contextual and interpersonal placebo responses. By viewing interpersonal healing as a central causal process (or a set of related causal processes) within the domain of pain modulation, it is possible to probe the potential role for OXT and AVP in the modulation of a placebo response. In pursuit of this goal, we use a neuropharmacological intervention with OXT and AVP agonists in combination with a behavioral, brain imaging and genetic approach.
Study population:
Healthy men and women participants aging from 18 to 55 years.
Design:
We will investigate the role of oxytocinergic system in the processing of social cues by using a model of pain and interpersonal placebo analgesia already tested (9). The following drugs will be used: 1) oxytocin, 2) arginine vasopressin, and 3) placebo.
Outcome measures:
Primary outcomes are subjective pain reports (Experiment 1) and brain- and cortical -related responses (Experiments 2 and 3). Secondary measures include skin conductance response, heart rate, cortisol, subjective measures of empathy; trait and state anxiety measures; and functional pain-related genetic polymorphisms.
Study design
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Men and Women
- Aged between 18-55 years
- Able to understand and speak the English language
Key exclusion criteria (26 listed)
- Any significant medical or neurological problems (e.g. cardiovascular illness, respiratory illness, neurologic illness, seizures, etc.)
- History of angioedema
- High blood pressure (above 140 mmHg) or symptomatic low blood pressure
- History of fainting
- A family history of mania, schizophrenia, or other psychoses (first-degree relatives only)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Not reported in the source record.
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jul 2018.
- Background: PubMed 15995725Colloca L, Benedetti F. Placebos and painkillers: is mind as real as matter? Nat Rev Neurosci. 2005 Jul;6(7):545-52. doi: 10.1038/nrn1705.
- Background: PubMed 17960416Colloca L, Benedetti F, Porro CA. Experimental designs and brain mapping approaches for studying the placebo analgesic effect. Eur J Appl Physiol. 2008 Mar;102(4):371-80. doi: 10.1007/s00421-007-0593-6. Epub 2007 Oct 25.
- Background: PubMed 19338509Zubieta JK, Stohler CS. Neurobiological mechanisms of placebo responses. Ann N Y Acad Sci. 2009 Mar;1156:198-210. doi: 10.1111/j.1749-6632.2009.04424.x.
- Derived from this study: PubMed 31350784Colloca L, Schenk LA, Nathan DE, Robinson OJ, Grillon C. When Expectancies Are Violated: A Functional Magnetic Resonance Imaging Study. Clin Pharmacol Ther. 2019 Dec;106(6):1246-1252. doi: 10.1002/cpt.1587. Epub 2019 Sep 10.
- Derived from this study: PubMed 24771206Colloca L, Grillon C. Understanding placebo and nocebo responses for pain management. Curr Pain Headache Rep. 2014 Jun;18(6):419. doi: 10.1007/s11916-014-0419-2.
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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.
Luana Colloca, M.D. principal investigator
National Institute of Mental Health (NIMH)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Placebo Analgesia, run by National Institute of Mental Health (NIMH) 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?
The sponsor lists 3 inclusion and 26 exclusion criteria. 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: stopped early, as of the sponsor's last update on 5 Jul 2018. 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. 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?
The study was stopped early. Results are not available in the source record.
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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01328561, which also lists 5 linked publications.
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 5 Jul 2018.