Drug EffectPhase 1NOANCT03801629
Neuroimmune Effects of Opioid Administration
A Phase 1 study testing High Morphine Dose and Low Morphine Dose in people with Drug Effect, run by Yale University at 1 site in United States.
Trial summary
Preclinical research indicates acute opioid administration evokes an immune response in the periphery and brain. Here, we will translate those preclinical findings to healthy human volunteers and quantify the neuroimmune response to a morphine challenge using positron emission tomography (PET) imaging with [11C]PBR28. Read more about this study
- Who is it for?
- Ages 21 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Drug Effect
- What is being tested?
- High Morphine Dose and Low Morphine Dose
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Sep 2019to 10 Mar 2021
- Phase
- Phase 1
- 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 21 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Men and women aged between 21 and 50 years (driver's license or valid state ID).
- Physically healthy by medical history, physical, neurological, EKG and laboratory examinations (reviewed by the Study Physician).
- Normal weight, as indicated by a body mass index (BMI) and body weight ≤ 250lbs.
- Read, comprehend, and write English at a sufficient level to complete study-related materials.
- Able to provide voluntary and written informed consent.
- Eligibility and willingness to participate in study procedures, including MRI and PET scanning.
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- Previous medical use of opioids without adverse reactions (≥2 lifetime uses).
- Medically eligible to receive up to 0.1 mg/kg deltoid intramuscular morphine (based on medical history, medical exams, and not meeting any exclusion criteria below).
- Medically eligible to receive 10mg of oral metoclopramide based on medical history, medical exams, and current medications.
Who cannot join
- Any DSM-5 Axis I disorder diagnosis based on Structured Clinical Interview for DSM-5 (SCID-5), including meeting criteria for substance dependence.
- Any current psychotropic medication use, including MAOI use within the past 14 days
- Recent (past 6 months) medical or non-medical opioid-use.
- Prior medical use prescription opioids for >14 consecutive days (self-report)
- Prior non-medical use of any opioid (i.e., recreational opioid use will be excluded).
- Positive result on a urine drug screen (excluding marijuana).
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- Current or previous chronic pain disorder (>6 months of continuous pain).
- 'Low affinity binding' individuals based on rs6971 polymorphism (<10% of the population).
- For females, pregnancy (positive urine test).
- Current use of non-steroidal anti-inflammatory medications or statins.
- Medical contraindication to receive up to 0.1 mg/kg intramuscular morphine administration as determined by Study Physician. This includes:
- known hypersensitivity/allergy to morphine;
- acute or severe bronchial asthma;
- known or suspected gastrointestinal obstruction, including paralytic ileus;
- seizure disorder;
- concomitant use of a benzodiazepine or any other CNS depressant;
- any other significant medical condition, that in the opinion of the Study Physician and Investigators, could: put the patient at risk because of participation in the study, or influence the results of the study, or cause concern about the patient's ability to successfully complete in the study.
- Known family history (first-degree relative) of opioid-use disorder or alcohol-use disorder.
- MRI contraindications, including metal in body (or work in metal/machine shop), pacemaker, claustrophobia, or inability to tolerate MRI scanning.
- Medical contraindications to metoclopramide, as determined by the Study Physician, including:
- known hypersensitivity/allergy to metoclopramide;
- mechanical gastrointestinal obstruction, perforation, or hemorrhage;
- seizure disorder;
- history of tardive dyskinesia;
- or concomitant use of medications/agents likely to increase extrapyramidal reactions.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Imaging the Neuroimmune Effects of Acute Opioid Administration
Preclinical research indicates acute opioid administration evokes an immune response in the periphery and brain. Here, we will translate those preclinical findings to healthy human volunteers and quantify the neuroimmune response to a morphine challenge using positron emission tomography (PET) imaging with [11C]PBR28.
Read the detailed description
Subjects will be recruited from the local community via media advertisements, flyers, and word-of-mouth. Interested individuals will undergo a phone screen and in-person medical and psychiatric examination. Up to 20 eligible individuals (see Inclusion/Exclusion criteria) will be invited to participate in this study.
In a single day, subjects will complete behavioral and physiological testing, a [11C]PBR28 PET scan, and report subjective drug effects before and after a morphine challenge. Subjects will complete either a 'High' or 'Low' morphine dose condition (single-blind): 0.07mg/kg i.m. vs. 0.04mg/kg i.m., respectively. To measure the neuroimmune response to morphine, we will use [11C]PBR28 PET imaging (120-minute scans on a High Resolution Research Tomograph with Vicra motion correction). [11C]PBR28 binds with high affinity and specificity to the 18kDa translocator protein (TSPO), which is highly expressed in microglia and has been shown to respond to inflammatory challenges. TSPO volumes of distribution (VT), i.e., TSPO availability, will be quantified in brain regions of interest using multilinear analysis-1 (MA-1) with the metabolite-corrected arterial input function. The post-morphine [11C]PBR28 PET scan will occur 2-hours after the morphine challenge.
Specific Aim 1: To determine whether an acute morphine administration increases brain TSPO availability in healthy volunteers.
Hypothesis 1: Relative to pre-morphine levels, morphine will significantly increase TSPO availability across brain regions of interest, consistent with a neuroimmune response.
Specific Aim 2: To determine whether morphine evokes a dose-dependent increase in brain TSPO availability in healthy volunteers.
Hypothesis 2: Relative to pre-morphine levels, morphine will dose-dependently increase TSPO availability across brain regions of interest.
Specific Aim 3: To determine whether morphine administration increases peripheral markers of inflammation, e.g., cytokine/chemokine concentration in plasma.
Hypothesis 3: Relative to pre-morphine levels, morphine will increase cytokine/chemokine concentrations in plasma, including IL-1B, IL-2, IL-6, IL-10, TNF-a, IFNy, MCP-1, and GM-CSF, consistent with a peripheral immune response. Exploratory Hypotheses: 1) IL-1B, IL-6, TNF-a, IFNy, MCP-1, and GM-CSF will exhibit morphine dose-dependent increases in plasma. 2) The change in IL-6, TNF-a, IFN-y, and GM-CSF levels will be positively correlated with the change in brain TSPO VT levels.
Specific Aim 4: To determine whether morphine administration alters pain sensitivity, pain tolerance, cognitive function, and reward responsiveness.
Hypothesis 4: Relative to pre-morphine levels, morphine will enhance pain tolerance and impair verbal learning/memory proficiency and impair reward responsiveness. Morphine will not alter pain sensitivity, visual attention, psychomotor processing speed, or working memory proficiency. Exploratory hypotheses: 1) The change in TSPO availability in thalamus will be positively correlated with the change in pain tolerance. 2) The change in TSPO availability in hippocampus will be inversely correlated with the change in verbal learning/memory proficiency. 3) The change in TSPO availability in caudate, ACC, and OFC will be inversely correlated with the change in reward responsiveness.
Specific Aim 5: To determine whether morphine administration alters vital signs.
Hypothesis 5: Relative to pre-morphine levels, morphine will dose-dependently reduce systolic and diastolic blood pressure. Relative to pre-morphine levels, morphine will lower heart rate.
Specific Aim 6: To measure the subjective response to morphine administration.
Hypothesis 6: Relative to pre-morphine levels, morphine will dose-dependently increase subjective ratings of 'high', 'good drug effect', 'nausea', and 'bad drug effect'. Exploratory hypotheses: 1) The change in TSPO availability in caudate, ACC, and OFC will be positively correlated with the change in 'high' and 'good drug effect'. 2) The change in TSPO availability in the insula and thalamus will be positively correlated with the change in 'nausea' and 'bad drug effect'.
Specific Aim 7: To determine whether morphine administration alters peripheral stress markers of the autonomic nervous system and HPA-axis.
Hypothesis 7: Relative to pre-morphine levels, morphine will dose-dependently increase plasma levels of epinephrine, norepinephrine, and cortisol.
Specific Aim 8: To determine whether morphine administration alters peripheral markers of neurosteroids.
Hypothesis 8: Relative to pre-morphine levels, morphine will dose-dependently increase plasma levels of allopregnanolone and pregnenolone.
Specific Aim 9: To determine whether morphine administration alters peripheral markers of the metabolic hormone ghrelin.
Hypothesis 9: Relative to pre-morphine levels, morphine will dose-dependently increase plasma levels of ghrelin.
- Conditions
- Drug Effect
- Being tested
- High Morphine Dose, Low Morphine Dose
- Keywords
- Neuroimmune System, Morphine, PET Imaging, TSPO
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
High Morphine DoseDrug
Also called High Dose
Subjects will receive an intramuscular morphine injection (0.07mg/kg) in the non-dominant deltoid muscle. Metoclopramide (10mg; oral) will be administered PRN to reduce nausea.
Low Morphine DoseDrug
Also called Low Dose
Subjects will receive an intramuscular morphine injection (0.04mg/kg) in the non-dominant deltoid muscle. Metoclopramide (10mg; oral) will be administered PRN to reduce nausea.
| Study group | Role | What they receive |
|---|---|---|
| High Morphine Dose | Experimental | Subjects in this experimental arm will receive a single intramuscular morphine dose (non-dominant deltoid muscle; 0.07 mg/kg). Receives: Drug: High Morphine Dose |
| Low Morphine Dose | Experimental | Subjects in this experimental arm will receive a single intramuscular morphine dose (non-dominant deltoid muscle; 0.04 mg/kg). Receives: Drug: Low Morphine Dose |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Brain TSPO availability
Relative to pre-morphine levels, we will measure the change in brain regional TSPO availability (VT) after morphine. VT will be calculated for brain regions of interest using multi-linear analysis 1 (t*=30) using the metabolite-corrected arterial input function.
Measured: One 120-minute PET [11C]PBR28 scan before and one PET [11C]PBR28 scan 2hr after morphine challenge.
Secondary outcomes (17)
Change in Verbal Learning Performance
Relative to pre-morphine levels, we will measure the change in verbal learning performance after morphine via the Cogstate computerized task: International Shopping List. In this task, subjects are asked to memorize and recite (without prompt) 12 common grocery shopping items across 3 trials. Number of correct items recalled across the 3 trials is analyzed.
Measured: This Cogstate task will be administered twice: once before and once ~40 minutes after the morphine challenge.
Change in Verbal Memory Performance
Relative to pre-morphine levels, we will measure the change in verbal memory performance after morphine via the Cogstate computerized task: International Shopping List - Delayed Recall. In this task, subjects are asked to recall (after a time delay) the 12 common grocery shopping items from the International Shopping List task. Number of correct items recalled in this one trial is analyzed.
Measured: This Cogstate task will be administered twice: once before and once ~70 minutes after the morphine challenge.
Change in Psychomotor Speed
Relative to pre-morphine levels, we will measure the change in psychomotor speed via the Cogstate computerized task: Detection. In this task, subjects are asked to respond via button press as soon as the playing card on screen flips over. The log10 of the mean latency to respond (ms) is analyzed.
Measured: This Cogstate task will be administered twice: once before and once ~45 minutes after the morphine challenge.
Change in Visual Attention
Relative to pre-morphine levels, we will measure the change in visual attention via the Cogstate computerized task: Identification. In this task, subjects are asked to respond via button press as soon as he/she identifies that the playing card on screen matches the target card color (red). The log10 of the mean latency to respond (ms) is analyzed.
Measured: This Cogstate task will be administered twice: once before and once ~50 minutes after the morphine challenge.
Change in Visual Learning
Relative to pre-morphine levels, we will measure the change in visual learning via the Cogstate computerized task: One Card Learning. In this task, subjects are asked to respond via button press if he/she identifies that the on-screen playing card has been shown previously. The arc sine of the percent correctly identified is analyzed.
Measured: This Cogstate task will be administered twice: once before and once ~55 minutes after the morphine challenge.
Change in Working Memory (easy)
Relative to pre-morphine levels, we will measure the change in working memory performance via the Cogstate computerized task: One Back. In this task, subjects are asked to respond via button press if he/she identifies that the on-screen playing card matches the card shown just prior to the current card. The log10 of the mean latency to respond (ms) is analyzed.
Measured: This Cogstate task will be administered twice: once before and once ~60 minutes after the morphine challenge.
Change in Working Memory (hard)
Relative to pre-morphine levels, we will measure the change in working memory performance via the Cogstate computerized task: Two Back. In this task, subjects are asked to respond via button press if he/she identifies that the on-screen playing card matches the card shown two prior to the current card. The arc sine of the percent correctly identified is analyzed.
Measured: This Cogstate task will be administered twice: once before and once ~65 minutes after the morphine challenge.
Change in Venous Cytokine/Chemokine Concentration
Relative to pre-morphine levels, we will measure the change in venous cytokine and chemokine concentrations (e.g., IL-6, IL-10, TNF-alpha, GM-CSF, and IFN-gamma) periodically after morphine via ELISA assay kit.
Measured: Plasma samples will be collected 10-minutes before and 60-minutes, 110-minutes, and 250-minutes after the morphine challenge.
Change in Venous Cortisol Concentration
Relative to pre-morphine levels, we will measure the change in venous cortisol levels periodically after morphine via ELISA assay kit.
Measured: Plasma samples will be collected 10-minutes before and 60-minutes, 110-minutes, and 250-minutes after the morphine challenge.
Change in Venous Epinephrine Concentration
Relative to pre-morphine levels, we will measure the change in venous epinephrine levels periodically after morphine via ELISA assay kit.
Measured: Plasma samples will be collected 10-minutes before and 60-minutes, 110-minutes, and 250-minutes after the morphine challenge.
Change in Venous Norepinephrine Concentration
Relative to pre-morphine levels, we will measure the change in venous norepinephrine levels periodically after morphine via ELISA assay kit.
Measured: Plasma samples will be collected 10-minutes before and 60-minutes, 110-minutes, and 250-minutes after the morphine challenge.
Change in Venous Allopregnanolone Concentration
Relative to pre-morphine levels, we will measure the change in venous allopregnanolone levels periodically after morphine via ELISA assay kit.
Measured: Plasma samples will be collected 10-minutes before and 60-minutes, 110-minutes, and 250-minutes after the morphine challenge.
Change in Venous Pregnenolone Concentration
Relative to pre-morphine levels, we will measure the change in venous pregnenolone levels periodically after morphine via ELISA assay kit.
Measured: Plasma samples will be collected 10-minutes before and 60-minutes, 110-minutes, and 250-minutes after the morphine challenge.
Change in Venous Ghrelin Concentration
Relative to pre-morphine levels, we will measure the change in venous ghrelin levels periodically after morphine via ELISA assay kit.
Measured: Plasma samples will be collected 10-minutes before and 60-minutes, 110-minutes, and 250-minutes after the morphine challenge.
Change in Thermal Pain Sensitivity
Relative to pre-morphine levels, we will measure the change in thermal pain sensitivity after morphine via the Cold Pressor Task. Subjects will place their hand in a warm water bath and then a cold water bath. Subjects will be asked to indicate when he/she first experiences pain related to the cold water bath. Time to detection of pain (s) is analyzed.
Measured: The Cold Pressor Task will be administered once before and once ~90-minutes after the morphine challenge.
Change in Thermal Pain Tolerance
Relative to pre-morphine levels, we will measure the change in thermal pain tolerance after morphine via the Cold Pressor Task. Subjects will place their hand in a warm water bath and then a cold water bath. Time to withdrawal his/her hand from the cold water bath (s; max: 90s) is analyzed.
Measured: The Cold Pressor Task will be administered once before and once ~90-minutes after the morphine challenge.
Change in Reward Responsiveness
Relative to pre-morphine levels, we will measure the change in reward responsiveness after morphine via the computerized Probabilistic Reward Task. Reward responsiveness is calculated as the subject's propensity to modulate his/her response latency to discriminate two stimuli (short and long mouths on a face) based on prior reinforcement (monetary reward for 'correct' responses). This task allows objective measurement of an individuals' responsiveness to monetary reward.
Measured: The Probabilistic Reward Task will be administered once before and once ~260 minutes after morphine.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jan 2019
- Study start12 Sep 2019
- Primary completion10 Mar 2021
- Study completion10 Mar 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Drug EffectStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- 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 1
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Subjects will receive a single intramuscular morphine dose: 'High' (0.07mg/kg i.m.) vs. 'Low' (0.04mg/kg i.m.)
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Eric Woodcock, Yale University
- Investigators
- Eric Woodcock, PhD, Principal investigator, Yale UniversityKelly Cosgrove, PhD, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03801629
- Sponsor's protocol ID
- 2000024785
- Acronym
- NOA
- Status last verified
- Apr 2021
- First submitted
- 8 Jan 2019
- Last updated
- 27 Apr 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified participant data will be shared upon reasonable request.
Study at a glance
From the registry record, last updated by the sponsor on 27 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Imaging the Neuroimmune Effects of Acute Opioid Administration
- ClinicalTrials.gov ID
- NCT03801629
- Acronym / sponsor ID
- NOA / 2000024785
- Conditions
- Drug Effect
- Keywords
- Neuroimmune System, Morphine, PET Imaging, TSPO
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Study start
- 12 Sep 2019 (actual)
- Primary completion
- 10 Mar 2021 (actual)
- Study completion
- 10 Mar 2021 (actual)
- First posted
- 11 Jan 2019 (actual)
- 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.
Preclinical research indicates acute opioid administration evokes an immune response in the periphery and brain. Here, we will translate those preclinical findings to healthy human volunteers and quantify the neuroimmune response to a morphine challenge using positron emission tomography (PET) imaging with [11C]PBR28.
Detailed description
Subjects will be recruited from the local community via media advertisements, flyers, and word-of-mouth. Interested individuals will undergo a phone screen and in-person medical and psychiatric examination. Up to 20 eligible individuals (see Inclusion/Exclusion criteria) will be invited to participate in this study.
In a single day, subjects will complete behavioral and physiological testing, a [11C]PBR28 PET scan, and report subjective drug effects before and after a morphine challenge. Subjects will complete either a 'High' or 'Low' morphine dose condition (single-blind): 0.07mg/kg i.m. vs. 0.04mg/kg i.m., respectively. To measure the neuroimmune response to morphine, we will use [11C]PBR28 PET imaging (120-minute scans on a High Resolution Research Tomograph with Vicra motion correction). [11C]PBR28 binds with high affinity and specificity to the 18kDa translocator protein (TSPO), which is highly expressed in microglia and has been shown to respond to inflammatory challenges. TSPO volumes of distribution (VT), i.e., TSPO availability, will be quantified in brain regions of interest using multilinear analysis-1 (MA-1) with the metabolite-corrected arterial input function. The post-morphine [11C]PBR28 PET scan will occur 2-hours after the morphine challenge.
Specific Aim 1: To determine whether an acute morphine administration increases brain TSPO availability in healthy volunteers.
Hypothesis 1: Relative to pre-morphine levels, morphine will significantly increase TSPO availability across brain regions of interest, consistent with a neuroimmune response.
Specific Aim 2: To determine whether morphine evokes a dose-dependent increase in brain TSPO availability in healthy volunteers.
Hypothesis 2: Relative to pre-morphine levels, morphine will dose-dependently increase TSPO availability across brain regions of interest.
Specific Aim 3: To determine whether morphine administration increases peripheral markers of inflammation, e.g., cytokine/chemokine concentration in plasma.
Hypothesis 3: Relative to pre-morphine levels, morphine will increase cytokine/chemokine concentrations in plasma, including IL-1B, IL-2, IL-6, IL-10, TNF-a, IFNy, MCP-1, and GM-CSF, consistent with a peripheral immune response. Exploratory Hypotheses: 1) IL-1B, IL-6, TNF-a, IFNy, MCP-1, and GM-CSF will exhibit morphine dose-dependent increases in plasma. 2) The change in IL-6, TNF-a, IFN-y, and GM-CSF levels will be positively correlated with the change in brain TSPO VT levels.
Specific Aim 4: To determine whether morphine administration alters pain sensitivity, pain tolerance, cognitive function, and reward responsiveness.
Hypothesis 4: Relative to pre-morphine levels, morphine will enhance pain tolerance and impair verbal learning/memory proficiency and impair reward responsiveness. Morphine will not alter pain sensitivity, visual attention, psychomotor processing speed, or working memory proficiency. Exploratory hypotheses: 1) The change in TSPO availability in thalamus will be positively correlated with the change in pain tolerance. 2) The change in TSPO availability in hippocampus will be inversely correlated with the change in verbal learning/memory proficiency. 3) The change in TSPO availability in caudate, ACC, and OFC will be inversely correlated with the change in reward responsiveness.
Specific Aim 5: To determine whether morphine administration alters vital signs.
Hypothesis 5: Relative to pre-morphine levels, morphine will dose-dependently reduce systolic and diastolic blood pressure. Relative to pre-morphine levels, morphine will lower heart rate.
Specific Aim 6: To measure the subjective response to morphine administration.
Hypothesis 6: Relative to pre-morphine levels, morphine will dose-dependently increase subjective ratings of 'high', 'good drug effect', 'nausea', and 'bad drug effect'. Exploratory hypotheses: 1) The change in TSPO availability in caudate, ACC, and OFC will be positively correlated with the change in 'high' and 'good drug effect'. 2) The change in TSPO availability in the insula and thalamus will be positively correlated with the change in 'nausea' and 'bad drug effect'.
Specific Aim 7: To determine whether morphine administration alters peripheral stress markers of the autonomic nervous system and HPA-axis.
Hypothesis 7: Relative to pre-morphine levels, morphine will dose-dependently increase plasma levels of epinephrine, norepinephrine, and cortisol.
Specific Aim 8: To determine whether morphine administration alters peripheral markers of neurosteroids.
Hypothesis 8: Relative to pre-morphine levels, morphine will dose-dependently increase plasma levels of allopregnanolone and pregnenolone.
Specific Aim 9: To determine whether morphine administration alters peripheral markers of the metabolic hormone ghrelin.
Hypothesis 9: Relative to pre-morphine levels, morphine will dose-dependently increase plasma levels of ghrelin.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
- Model description
- Subjects will receive a single intramuscular morphine dose: 'High' (0.07mg/kg i.m.) vs. 'Low' (0.04mg/kg i.m.)
| Arm | Type | Receives |
|---|---|---|
| High Morphine Dose | Experimental | Drug: High Morphine DoseSubjects in this experimental arm will receive a single intramuscular morphine dose (non-dominant deltoid muscle; 0.07 mg/kg). |
| Low Morphine Dose | Experimental | Drug: Low Morphine DoseSubjects in this experimental arm will receive a single intramuscular morphine dose (non-dominant deltoid muscle; 0.04 mg/kg). |
Who may qualify
- Ages
- 21 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- Men and women aged between 21 and 50 years (driver's license or valid state ID).
- Physically healthy by medical history, physical, neurological, EKG and laboratory examinations (reviewed by the Study Physician).
- Normal weight, as indicated by a body mass index (BMI) and body weight ≤ 250lbs.
- Read, comprehend, and write English at a sufficient level to complete study-related materials.
- Able to provide voluntary and written informed consent.
Key exclusion criteria (25 listed)
- Any DSM-5 Axis I disorder diagnosis based on Structured Clinical Interview for DSM-5 (SCID-5), including meeting criteria for substance dependence.
- Any current psychotropic medication use, including MAOI use within the past 14 days
- Recent (past 6 months) medical or non-medical opioid-use.
- Prior medical use prescription opioids for >14 consecutive days (self-report)
- Prior non-medical use of any opioid (i.e., recreational opioid use will be excluded).
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 |
|---|---|---|
| High Morphine DoseAlso: High DoseSubjects will receive an intramuscular morphine injection (0.07mg/kg) in the non-dominant deltoid muscle. Metoclopramide (10mg; oral) will be administered PRN to reduce nausea. | Drug | High Morphine Dose |
| Low Morphine DoseAlso: Low DoseSubjects will receive an intramuscular morphine injection (0.04mg/kg) in the non-dominant deltoid muscle. Metoclopramide (10mg; oral) will be administered PRN to reduce nausea. | Drug | Low Morphine Dose |
Primary outcome
Change in Brain TSPO availability
Time frame: One 120-minute PET [11C]PBR28 scan before and one PET [11C]PBR28 scan 2hr after morphine challenge.
Relative to pre-morphine levels, we will measure the change in brain regional TSPO availability (VT) after morphine. VT will be calculated for brain regions of interest using multi-linear analysis 1 (t*=30) using the metabolite-corrected arterial input function.
17 secondary outcomes
Change in Verbal Learning Performance
Time frame: This Cogstate task will be administered twice: once before and once ~40 minutes after the morphine challenge.
Change in Verbal Memory Performance
Time frame: This Cogstate task will be administered twice: once before and once ~70 minutes after the morphine challenge.
Change in Psychomotor Speed
Time frame: This Cogstate task will be administered twice: once before and once ~45 minutes after the morphine challenge.
Change in Visual Attention
Time frame: This Cogstate task will be administered twice: once before and once ~50 minutes after the morphine challenge.
Change in Visual Learning
Time frame: This Cogstate task will be administered twice: once before and once ~55 minutes after the morphine challenge.
Change in Working Memory (easy)
Time frame: This Cogstate task will be administered twice: once before and once ~60 minutes after the morphine challenge.
Change in Working Memory (hard)
Time frame: This Cogstate task will be administered twice: once before and once ~65 minutes after the morphine challenge.
Change in Venous Cytokine/Chemokine Concentration
Time frame: Plasma samples will be collected 10-minutes before and 60-minutes, 110-minutes, and 250-minutes after the morphine challenge.
Change in Venous Cortisol Concentration
Time frame: Plasma samples will be collected 10-minutes before and 60-minutes, 110-minutes, and 250-minutes after the morphine challenge.
Change in Venous Epinephrine Concentration
Time frame: Plasma samples will be collected 10-minutes before and 60-minutes, 110-minutes, and 250-minutes after the morphine challenge.
Change in Venous Norepinephrine Concentration
Time frame: Plasma samples will be collected 10-minutes before and 60-minutes, 110-minutes, and 250-minutes after the morphine challenge.
Change in Venous Allopregnanolone Concentration
Time frame: Plasma samples will be collected 10-minutes before and 60-minutes, 110-minutes, and 250-minutes after the morphine challenge.
Change in Venous Pregnenolone Concentration
Time frame: Plasma samples will be collected 10-minutes before and 60-minutes, 110-minutes, and 250-minutes after the morphine challenge.
Change in Venous Ghrelin Concentration
Time frame: Plasma samples will be collected 10-minutes before and 60-minutes, 110-minutes, and 250-minutes after the morphine challenge.
Change in Thermal Pain Sensitivity
Time frame: The Cold Pressor Task will be administered once before and once ~90-minutes after the morphine challenge.
Change in Thermal Pain Tolerance
Time frame: The Cold Pressor Task will be administered once before and once ~90-minutes after the morphine challenge.
Change in Reward Responsiveness
Time frame: The Probabilistic Reward Task will be administered once before and once ~260 minutes after morphine.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Apr 2021.
- Individual participant dataSharing planned: Yes. De-identified participant data will be shared upon reasonable request.
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Recruiting
Stress Reduction and Lifestyle Modification in Irritable Bowel Syndrome Patients
Irritable Bowel Syndrome
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.
Eric Woodcock, PhD principal investigator
Yale University
Kelly Cosgrove, PhD principal investigator
Yale University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing High Morphine Dose and Low Morphine Dose in people with Drug Effect, run by Yale University 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 9 inclusion and 25 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 27 Apr 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?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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 Brain TSPO availability (time frame: One 120-minute PET [11C]PBR28 scan before and one PET [11C]PBR28 scan 2hr after morphine challenge.). 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 27 Apr 2021.