PainEarly Phase 1NCT03096353
Sensory and Opioid Mechanisms of Affective Touch
A Early Phase 1 study testing Naloxone in people with Pain and Touch, run by National Center for Complementary and Integrative Health (NCCIH) at 1 site in United States.
Trial summary
Background: Medicines called opioids are used to treat pain. The body also produces opioids. These are called endorphins. Researchers want to learn more about how these natural opioids work. This might lead to new therapies for conditions like depression, anxiety, and chronic pain. Read more about this study
- Who is it for?
- Ages 18 to 50 years
- What is being tested?
- Naloxone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 29 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Aug 2017to 31 Oct 2018
- Phase
- Early Phase 1
- 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 50 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
None listed.
Who cannot join
- Overall exclusion criteria for the study:
- Unable to comply with study procedures (or does not rate stimuli as tolerable) or unable to schedule visits promptly (including inability to schedule the second session within approximately 14 days of the first session)
- Pregnancy or breastfeeding.
- Use of recreational drugs in the past month (e.g., marijuana, methylenedioxymethamphetamine (MDMA, 'ecstasy' or 'Molly'), Lysergic acid diethylamide (LSD), cocaine, methamphetamine, heroin, prescription and/or opioids).
- Congenital lower limb deficiency or amputation.
- Peripheral neuropathy, dermatological condition such as scars or burns, or has had a tattoo in the testing region within the previous four weeks that might influence cutaneous sensibility.
Show all 22Show fewer
- Women who consume more than 7 alcoholic beverages per week, and men who consume more than 14 drinks per week.
- Current chronic pain condition or has had chronic pain in the past year (painful condition lasting more than six months), including ongoing treatment with medications for neuropathic pain (e.g. gabapentin, tricyclic antidepressants, pregabalin, tramadol)
- Major medical condition, such as kidney, liver, cardiovascular (including blood clots, hypertension, preexisting cardiac arrhythmia), autonomic, pulmonary, or neurological problems (e.g., seizure disorder ) or a chronic systemic disease (e.g., diabetes).
- Current diagnosis or pharmacological treatment of psychiatric disorders such as major depression, major anxiety-related problems, post-traumatic stress syndrome, bipolar disorder, psychosis, attention-deficit/hyperactivity disorder or current or lifetime alcohol or substance abuse disorders (as identified in study #16-AT-0077)
- Participant has metal in his/her body which would make having an MRI scan unsafe, such as pacemakers, medication pumps, aneurysm clips, metallic prostheses (including metal pins and rods, heart valves or cochlear implants), shrapnel fragments, permanent eye liner or small metal fragments in the eye that welders and other metal workers may have.
- Participant is uncomfortable in small closed spaces (has claustrophobia) so that he/she would feel uncomfortable in the MRI machine or cannot lie comfortably flat on his/her back for up to 75 minutes in the MRI scanner.
- Participants weighs more than 550 lbs.
- Participant has taken any pain medication other than an over-the-counter NSAIDs or acetaminophen within the last month or for more than one month on a continual basis within last six months.
- Previous participation in 13-AT-0143 (related study).
- NIH employees who are subordinates, relatives, or co-workers of the investigators, or NCCIH Division of Intramural Research (DIR) employees.
- Participants using medications that play into opioid pathways (e.g. loperamide or dextromethorphan), that could potentially interact with naloxone (naltrexone, methylnaltrexone, droperidol, fenfluramine and clonidine)
- Participant using any herbal supplements (such as yohimbine) due to risk of unknown dangerous interaction as there is no data for herbal preparations and naloxone.
- Participant has allergies to naloxone or similar drugs.
- Has consumed alcohol within 24 hours, shows signs of alcohol withdrawal syndrome, or has behavioral signs of intoxication will be excluded immediately and not have the possibility to reschedule their session.
- Used topical pain-relieving creams in the testing area (e.g. methylsalicylate, capsaicin) within 24 hours of testing or used non-steroidal anti-inflammatory drugs (NSAIDS, e.g. aspirin, ibuprofen), acetaminophen, or naproxen within 3 days of testing*.
- To be determined during the pre-session screening. Participants who cannot refrain from these activities may have their session rescheduled up to two times. If the participant is found non-compliant during the second rescheduled appointment, he or she will be excluded from the study.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Background:
Medicines called opioids are used to treat pain. The body also produces opioids. These are called endorphins. Researchers want to learn more about how these natural opioids work. This might lead to new therapies for conditions like depression, anxiety, and chronic pain.
Read more
Objective:
To determine how opioids affect how pleasant or unpleasant it feels when the skin is touched, compressed, or heated.
Eligibility:
Healthy right-handed adults ages 18-50.
Design:
Participants will be screened under another protocol.
Participants will have 2 study visits with the same procedures, at least 1 day apart. Each visit will last 3-4 hours.
Participants will wear shorts or change into scrubs so researchers can test on their legs.
Participants will answer questions and have urine tests.
Participants will have a brain magnetic resonance imaging (MRI) scan. The scanner is a metal cylinder in a strong magnetic field. Participants will lie on a table that slides in and out of the cylinder. A device called a coil will be placed over the head.
During MRI, participants will have sensory testing. They will get several types of touch to the calf of the leg. These include gentle brushing of the skin, gentle compression of the calf with an inflation sleeve, and heat stimuli.
Participants will have an intravenous line placed each day. They will get naloxone 1 day and saline the other day. Participants will not be told which they get. Naloxone is a drug that blocks opioid receptors.
The MRI and sensory testing will then be repeated.
After each stimuli block, participants will rate the sensations as well as their mood and calmness/anxiety.
Read the detailed description
Objective: Our recent pilot study found evidence suggesting that blocking endogenous opioid release increases the pleasantness associated with having the skin stroked. Deep pressure touch (observed in hugs and massage) also typically conveys a sense of pleasantness. This increased pleasantness contrasts with evidence that blocking endogenous opioid release increases pain. The current study will examine the role of endogenous opioids in the pleasantness of light skin stroking and deep pressure touch, and contrast it with their role in the unpleasantness of a painful heat stimulus. Further, it will examine the neural basis of observed perceptual changes, using fMRI. This study constitutes the first study of the K99 phase of a K99/R00 grant application recently submitted to National Center for Complementary and Integrative Health (NCCIH) by Dr. Laura Case.
Study Population: 30 healthy participants will be enrolled in the study.
Design: Participants will receive intravenous saline or intravenous naloxone on separate days to investigate the effect of mu-opioid antagonism on the intensity and pleasantness of superficial and deep affective touch and the intensity and unpleasantness of cutaneous heat pain. Using a double-blind cross-over design, functional Magnetic Resonance Imaging (fMRI) will be conducted during sensory testing before and after the infusion of each drug to examine the neural mediation of opioid effects on touch perception. Ratings of mood, anxiety, pain intensity, pleasantness/unpleasantness, wanting and liking will also be collected throughout the study session.
Outcome measures: We will compare subjective ratings (mood, calmness, anxiety, pleasantness, wanting, liking, pain intensity and unpleasantness) during naloxone and saline to: 1) Determine whether naloxone increases the pleasantness and/or intensity of affective touch (light brush and deep compression); 2) Determine whether naloxone increases the unpleasantness and/or intensity of cutaneous heat pain; 3) Determine the role of mood or anxiety changes in mediating the effect of endogenous opioids on these perceptual measures; 3) Determine changes in the brain activation related to these effects.
- Being tested
- Placebo, Naloxone
- Keywords
- NALOXONE, fMRI, Functional Magnetic Resonance Imaging (fMRI)
- Medical subject headings
- Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboOther
saline
NaloxoneDrug
We will be using naloxone at normal clinical doses as the study drug. Naloxone is an opiate antagonist and has been used since the 1960 s to reverse the effects of opiate overdoses.
| Study group | Role | What they receive |
|---|---|---|
| Naloxone, then Placebo | Experimental | Day one - During MRI session participant underwent sensory stimulus testing followed by bolus and infusion doses of naloxone (0.05 mg/kg bodyweight). When infusion levels reached stability, sensory testing was performed again.
Day two - During MRI session participant underwent sensory stimulus testing followed by bolus and infusion doses of normal saline. When infusion levels reached stability, sensory testing was performed again. Receives: Other: Placebo; Drug: Naloxone |
| Placebo, then Naloxone | Experimental | Day one - During MRI session participant underwent sensory stimulus testing followed by bolus and infusion doses of normal saline. When infusion levels reached stability, sensory testing was performed again.
Day two - During MRI session participant underwent sensory stimulus testing followed by bolus and infusion doses of naloxone (0.05 mg/kg bodyweight). When infusion levels reached stability, sensory testing was performed again. Receives: Other: Placebo; Drug: Naloxone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Pleasantness of Skin Brushing From Before to After Infusion
Measurement of brushing pleasantness using a visual analogue scale. Sensory hedonics (unpleasantness vs. pleasantness) was assessed on a scale ranging from extremely unpleasant (-100) to neutral (0), to extremely pleasant (100).
Measured: One day, within a 2 hour session
Secondary outcomes (5)
Changes in Pleasantness of Deep Skin Pressure From Before to After Infusion
Measurement of pressure pleasantness/unpleasantness using a visual analogue scale. Sensory hedonics (unpleasantness vs. pleasantness) was assessed on a scale ranging from extremely unpleasant (-100) to neutral (0), to extremely pleasant (100).
Measured: One day, within a 2 hour session
Change in Unpleasantness of Cutaneous Heat Pain From Before to After Infusion
Measurement of heat pleasantness/unpleasantness using a visual analogue scale. Sensory hedonics (unpleasantness vs. pleasantness) was assessed on a scale ranging from extremely unpleasant (-100) to neutral (0), to extremely pleasant (100).
Measured: One day, within a 2 hour session
Changes in Intensity of Skin Brushing From Before to After Infusion
Measurement of brushing intensity using a visual analogue scale. Intensity was assessed on a scale ranging from no sensation (-100) to pain threshold (0), to intolerable pain (100).
Measured: One day, within a 2 hour session
Changes in Intensity of Deep Skin Pressure From Before to After Infusion
Measurement of pressure intensity using a visual analogue scale. Intensity was assessed on a scale ranging from no sensation (-100) to pain threshold (0), to intolerable pain (100).
Measured: One day, within a 2 hour session
Changes in Intensity of Cutaneous Heat Pain From Before to After Infusion
Measurement of heat intensity using a visual analogue scale. Intensity was assessed on a scale ranging from no sensation (-100) to pain threshold (0), to intolerable pain (100).
Measured: One day, within a 2 hour session
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Mar 2017
- Study start1 Aug 2017
- Primary completion31 Oct 2018
- Study completion31 Oct 2018
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
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Center for Complementary and Integrative Health (NCCIH)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Catherine Bushnell, Ph.D., Principal investigator, National Center for Complementary and Integrative Health (NCCIH)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03096353
- Sponsor's protocol ID
- 170075
- Other IDs
- 17-AT-0075
- Status last verified
- Jun 2021
- First submitted
- 29 Mar 2017
- Last updated
- 30 Jul 2021
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sensory and Opioid Mechanisms of Affective Touch
- ClinicalTrials.gov ID
- NCT03096353
- Acronym / sponsor ID
- 170075
- Keywords
- NALOXONE, fMRI, Functional Magnetic Resonance Imaging (fMRI)
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- National Center for Complementary and Integrative Health (NCCIH)US National Institutes of Health
- Study start
- 1 Aug 2017 (actual)
- Primary completion
- 31 Oct 2018 (actual)
- Study completion
- 31 Oct 2018 (actual)
- First posted
- 30 Mar 2017 (actual)
- Results
- Posted 14 Jul 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
Medicines called opioids are used to treat pain. The body also produces opioids. These are called endorphins. Researchers want to learn more about how these natural opioids work. This might lead to new therapies for conditions like depression, anxiety, and chronic pain.
Objective:
To determine how opioids affect how pleasant or unpleasant it feels when the skin is touched, compressed, or heated.
Eligibility:
Healthy right-handed adults ages 18-50.
Design:
Participants will be screened under another protocol.
Participants will have 2 study visits with the same procedures, at least 1 day apart. Each visit will last 3-4 hours.
Participants will wear shorts or change into scrubs so researchers can test on their legs.
Participants will answer questions and have urine tests.
Participants will have a brain magnetic resonance imaging (MRI) scan. The scanner is a metal cylinder in a strong magnetic field. Participants will lie on a table that slides in and out of the cylinder. A device called a coil will be placed over the head.
During MRI, participants will have sensory testing. They will get several types of touch to the calf of the leg. These include gentle brushing of the skin, gentle compression of the calf with an inflation sleeve, and heat stimuli.
Participants will have an intravenous line placed each day. They will get naloxone 1 day and saline the other day. Participants will not be told which they get. Naloxone is a drug that blocks opioid receptors.
The MRI and sensory testing will then be repeated.
After each stimuli block, participants will rate the sensations as well as their mood and calmness/anxiety.
Detailed description
Objective: Our recent pilot study found evidence suggesting that blocking endogenous opioid release increases the pleasantness associated with having the skin stroked. Deep pressure touch (observed in hugs and massage) also typically conveys a sense of pleasantness. This increased pleasantness contrasts with evidence that blocking endogenous opioid release increases pain. The current study will examine the role of endogenous opioids in the pleasantness of light skin stroking and deep pressure touch, and contrast it with their role in the unpleasantness of a painful heat stimulus. Further, it will examine the neural basis of observed perceptual changes, using fMRI. This study constitutes the first study of the K99 phase of a K99/R00 grant application recently submitted to National Center for Complementary and Integrative Health (NCCIH) by Dr. Laura Case.
Study Population: 30 healthy participants will be enrolled in the study.
Design: Participants will receive intravenous saline or intravenous naloxone on separate days to investigate the effect of mu-opioid antagonism on the intensity and pleasantness of superficial and deep affective touch and the intensity and unpleasantness of cutaneous heat pain. Using a double-blind cross-over design, functional Magnetic Resonance Imaging (fMRI) will be conducted during sensory testing before and after the infusion of each drug to examine the neural mediation of opioid effects on touch perception. Ratings of mood, anxiety, pain intensity, pleasantness/unpleasantness, wanting and liking will also be collected throughout the study session.
Outcome measures: We will compare subjective ratings (mood, calmness, anxiety, pleasantness, wanting, liking, pain intensity and unpleasantness) during naloxone and saline to: 1) Determine whether naloxone increases the pleasantness and/or intensity of affective touch (light brush and deep compression); 2) Determine whether naloxone increases the unpleasantness and/or intensity of cutaneous heat pain; 3) Determine the role of mood or anxiety changes in mediating the effect of endogenous opioids on these perceptual measures; 3) Determine changes in the brain activation related to these effects.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Naloxone, then Placebo | Experimental | Other: Placebo, Drug: NaloxoneDay one - During MRI session participant underwent sensory stimulus testing followed by bolus and infusion doses of naloxone (0.05 mg/kg bodyweight). When infusion levels reached stability, sensory testing was performed again. Day two - During MRI session participant underwent sensory stimulus testing followed by bolus and infusion doses of normal saline. When infusion levels reached stability, sensory testing was performed again. |
| Placebo, then Naloxone | Experimental | Other: Placebo, Drug: NaloxoneDay one - During MRI session participant underwent sensory stimulus testing followed by bolus and infusion doses of normal saline. When infusion levels reached stability, sensory testing was performed again. Day two - During MRI session participant underwent sensory stimulus testing followed by bolus and infusion doses of naloxone (0.05 mg/kg bodyweight). When infusion levels reached stability, sensory testing was performed again. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (0 listed)
Key exclusion criteria (22 listed)
- Unable to comply with study procedures (or does not rate stimuli as tolerable) or unable to schedule visits promptly (including inability to schedule the second session within approximately 14 days of the first session)
- Pregnancy or breastfeeding.
- Use of recreational drugs in the past month (e.g., marijuana, methylenedioxymethamphetamine (MDMA, 'ecstasy' or 'Molly'), Lysergic acid diethylamide (LSD), cocaine, methamphetamine, heroin, prescription and/or opioids).
- Congenital lower limb deficiency or amputation.
- Peripheral neuropathy, dermatological condition such as scars or burns, or has had a tattoo in the testing region within the previous four weeks that might influence cutaneous sensibility.
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 |
|---|---|---|
| Placebosaline | Other | Naloxone, then Placebo, Placebo, then Naloxone |
| NaloxoneWe will be using naloxone at normal clinical doses as the study drug. Naloxone is an opiate antagonist and has been used since the 1960 s to reverse the effects of opiate overdoses. | Drug | Naloxone, then Placebo, Placebo, then Naloxone |
Primary outcome
Change in Pleasantness of Skin Brushing From Before to After Infusion
Time frame: One day, within a 2 hour session
Measurement of brushing pleasantness using a visual analogue scale. Sensory hedonics (unpleasantness vs. pleasantness) was assessed on a scale ranging from extremely unpleasant (-100) to neutral (0), to extremely pleasant (100).
5 secondary outcomes
Changes in Pleasantness of Deep Skin Pressure From Before to After Infusion
Time frame: One day, within a 2 hour session
Change in Unpleasantness of Cutaneous Heat Pain From Before to After Infusion
Time frame: One day, within a 2 hour session
Changes in Intensity of Skin Brushing From Before to After Infusion
Time frame: One day, within a 2 hour session
Changes in Intensity of Deep Skin Pressure From Before to After Infusion
Time frame: One day, within a 2 hour session
Changes in Intensity of Cutaneous Heat Pain From Before to After Infusion
Time frame: One day, within a 2 hour session
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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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.
Catherine Bushnell, Ph.D. principal investigator
National Center for Complementary and Integrative Health (NCCIH)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Naloxone in people with Pain and Touch, run by National Center for Complementary and Integrative Health (NCCIH) 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 0 inclusion and 22 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: finished, as of the sponsor's last update on 30 Jul 2021. 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.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Jul 2021). 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?
Change in Pleasantness of Skin Brushing From Before to After Infusion (time frame: One day, within a 2 hour session). 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 30 Jul 2021.