Sensory and Opioid Mechanisms of Affective Touch

NCT03096353 | Completed Early Phase 1 Results FDA Drug

• 2 other identifiers: 17007517-AT-0075
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Pain; Touch

Keywords

NALOXONE; fMRI; Functional Magnetic Resonance Imaging (fMRI)

Outcome Measures

Primary Outcomes (1)

• 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).

  One day, within a 2 hour session

Secondary Outcomes (5)

• Changes in Pleasantness of Deep Skin Pressure From Before to After Infusion

  One day, within a 2 hour session

• Change in Unpleasantness of Cutaneous Heat Pain From Before to After Infusion

  One day, within a 2 hour session

• Changes in Intensity of Skin Brushing From Before to After Infusion

  One day, within a 2 hour session

• Changes in Intensity of Deep Skin Pressure From Before to After Infusion

  One day, within a 2 hour session

• Changes in Intensity of Cutaneous Heat Pain From Before to After Infusion

  One day, within a 2 hour session

Other Outcomes (8)

• Activation in Somatosensory Cortex (S2) Brain Area of Interest (ROI) During Brushing

  One day, within a 2 hour session

• Activation in Somatosensory Cortex (S2) Brain Area of Interest (ROI) During Pressure

  One day, within a 2 hour session

• Changes in Mood During Skin Brushing From Before to After Infusion

  One day, within a 2 hour session

Study Arms (2)

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.

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.

Other: Placebo; Drug: Naloxone

Interventions

Placebo OTHER

saline

Naloxone, then Placebo; Placebo, then Naloxone

Naloxone DRUG

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.

Naloxone, then Placebo; Placebo, then Naloxone

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• All subjects must be:
• Between 18 and 50 years old.
• Right-handed (on Edinburgh Handedness Inventory).
• Fluent in English.
• Able to provide written informed consent.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• National Center for Complementary and Integrative Health (NCCIH): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Pain

Interventions

Naloxone

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Results Point of Contact

• Title: Catherine Bushnell
• Organization: National Center for Complementary and Integrative Health

mary.bushnell@nih.gov

+1 301 496 2222

Study Officials

• Catherine Bushnell, Ph.D.

  National Center for Complementary and Integrative Health (NCCIH)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 29, 2017
• First Posted: March 30, 2017
• Study Start: August 1, 2017
• Primary Completion: October 31, 2018
• Study Completion: October 31, 2018
• Last Updated: July 30, 2021
• Results First Posted: July 14, 2021

Record last verified: 2021-06

Locations

US (1)