A Phase 2 interventional study of MN-166 (50 mg) First and Placebo First in Opioid Abuse and Opioid Dependence, sponsored by New York State Psychiatric Institute. Completed at 1 site in United States. Open to participants aged 21 Years to 55 Years. Per ClinicalTrials.gov, last updated 2017-08-17.
Sponsored by New York State Psychiatric Institute · Phase 2, Interventional, and Other
Opioid drugs increase glial cell activation which may be related to the abuse liability of opioid drugs. Data supporting this hypothesis have demonstrated that glial cell attenuators decrease the positive rewarding aspect of opioids in laboratory animals. Ibudilast (MN-166, formerly AV411) is a compound that inhibits the activation of glia. Recent preclinical studies demonstrate that while ibudilast increases the analgesic effects of opioids, it decreases the rewarding effects of such drugs. It has also been shown that ibudilast suppresses morphine-induced release of dopamine, a primary neurotransmitter involved in the rewarding and reinforcing effects of abused drugs. Additionally, we recently found that ibudilast decreases subjective symptoms of opioid withdrawal in opioid dependent humans during detoxification.
Therefore, the primary aim of this 6-7 week inpatient study is to investigate the ability of MN-166 to dose-dependently alter the reinforcing, analgesic, subjective, performance, and physiological effects of oxycodone, a commonly abused prescription opioid.
This study includes a 10-day morphine taper phase, followed by two study phases (approximately 18 days each) with daily active ibudilast and placebo administration, respectively. After the detoxification phase, participants are randomized to receive placebo or MN-166, and then be stabilized on the medication. Thereafter, participants will complete laboratory sessions. Subsequently, during Phase 2, participants will cross over to the other treatment arm, stabilize, and complete laboratory sessions.
Opioid drugs increase glial cell activation and consequent cytokine release. These changes in glial cell activation may be related to the abuse liability of opioid drugs including heroin and prescription opioids. Data supporting this hypothesis have demonstrated that glial cell attenuators decrease the positive rewarding aspect of opioids in laboratory animals. Ibudilast (MN-166, formerly AV411) is a compound that inhibits the activation of glia and thereby inhibits the release of cytokines. Recent preclinical studies demonstrate that while ibudilast increases the analgesic effects of opioids, it decreases the rewarding effects of such drugs. It has also been shown that ibudilast suppresses morphine-induced release of dopamine, a primary neurotransmitter involved in the rewarding and reinforcing effects of abused drugs. Additionally, we recently found that ibudilast decreases subjective symptoms of opioid withdrawal in opioid dependent humans during detoxification.
Therefore, the primary aim of this 6-7 week inpatient study is to investigate the ability of MN-166 to dose-dependently alter the reinforcing, analgesic, subjective, performance, and physiological effects of oxycodone, a commonly abused prescription opioid. A secondary aim is to verify the ability of the drug to decrease opioid withdrawal symptoms during the initial inpatient detoxification.
This inpatient study includes a detoxification and two 18-day study phases. Upon study initiation, participants are tapered with morphine before study phase 1 starts, when they are randomized to receive placebo or 50 mg MN-166 BID (po at 0800 and 2000 hr), and then switched and stabilized on the medication. Thereafter, participants will complete 6 laboratory sessions over 9-10 days.
Subsequently, during Phase 2, participants will cross over to the other study arm (Pbo to MN-166 or MN-166 to Pbo), stabilize, and complete again 6 laboratory sessions. Days 1-10 of the study include a morphine taper, while each of the two subsequent study phases consist of a 7-8-day medication switch and stabilization phase, followed by 6 laboratory sessions over the next 9-10 days (3 sample sessions and 3 choice sessions). During sample sessions, participants will receive one dose of oxycodone (0, 15, or 30 mg/70 kg, PO) that will be available during the choice session the following day. At least 72 hrs after the previous sample session, the second sample session will be completed, followed by a choice session the next day. And then at least 72 hrs after the second sample session, the third and final sample session will be completed, followed by the final choice session the next day. The analgesic, subjective, performance, and physiological effects of oxycodone will be measured. During the choice session, a drug versus money self-administration paradigm will be employed, and the progressive ratio that is completed for drug and/or money will be measured.
We hypothesize that MN-166 will dose-dependently decrease oxycodone self-administration and positive subjective responses while increasing the analgesic effects of the drug.
A secondary additional objective is to collect exploratory information on potential predictors of prescription opioid self-administration including genetic polymorphisms, neurocognitive functioning, and response to stress. Blood samples will be collected to measure various genetic markers hypothesized to contribute to opioid drug effects (e.g., OPRM1, OPRD1, OPRK1, PENK, PDYN, DRD2, CYP3A4, and CYP2D6 genes). Performance on neurocognitive tasks and physiological response to the Trier Social Stress Test will be assessed in all participants.
1,411 studies on the registry are indexed under Opioid-Related Disorders; 290 are open to participants now.
This study's enrollment of 28 is below the median of 63 across 1,123 interventional studies indexed under Opioid-Related Disorders.
Browse Opioid-Related Disorders studies →New York State Psychiatric Institute is the lead sponsor of 425 studies on the registry; 26 are open to participants now.
Of its 50 completed or terminated interventional studies of FDA-regulated products, 45 (90%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Participants who began 14-day maintenance on MN-166 (50 mg) first, before switching to Placebo maintenance.
Drug: MN-166 (50 mg) First
Participants who began 14-day maintenance on Placebo first, before switching to MN-166 (50 mg) maintenance.
Drug: Placebo First
In this arm of the study participants were first maintained on 50 mg MN-166 BID for approximately 14 days, and were then switched onto placebo maintenance. The subjective and analgesic effects of Oxycodone (0 mg, 15 mg and 30 mg) were tested under each of the two maintenance conditions (Placebo \& MN-166).
Also known as: ibudilast/AV411
This arm of the study participants were first maintained on placebo for approximately 14 days, and were then switched onto 50mg MN-166 BID maintenance. . The subjective and analgesic effects of Oxycodone (0 mg, 15 mg and 30 mg) were tested under each of the two maintenance conditions (Placebo \& MN-166).
Also known as: placebo
Drug Self-administration Breakpoint
Participants are allowed to perform an operant task (click on a mouse) in order to receive a dose drug under investigation (oxycodone dose 0 mg, 15 mg, or 30 mg). The drug breakpoint is the maximum number of responses (mouse clicks) the participant was willing to make to receive the drug. Within the context of abuse liability studies, larger breakpoints represent greater abuse potential of a drug.
Time frame: 42 days
Positive Subjective Effects to Oxycodone
Participants are shown a 100-mm line and asked to indicate on that line the extent to which they agree with the descriptor of the drug effect such as "Liking/Liked the Drug." On this visual analog scale participants were instructed that the Left/ 0 mm point on the line represents "not at all," while the right/100 mm point represents "Extremely."
Time frame: 42 days
Pain Intensity
15-item shortened form of the McGill Pain Questionnaire (Melzack, 1987) that is used to assess the sensory and affective dimensions of the pain experienced Participants describe their experience of pain by choosing among a series of possible answers (None \[score=1\], Mild \[score=2\], Moderate \[score=3\], or Severe \[score=4\]). They were asked to describe the pain as "Throbbing," "Shooting," "Stabbing," "Sharp," "Cramping," "Gnawing," "Hot-Burning," "Aching," "Heavy," "Tender," "Splitting," "Tired-Exhausting," "Sickening," "Fearful," and "Punishing-Cruel." Scores were added across all 15 items to generate a sum score, which ranged between 15 and 60.
Time frame: 42 days
| Milestone | MN-166 First | Placebo First |
|---|---|---|
| Started | 12 | 16 |
| Completed | 3 | 8 |
| Not completed | 9 | 8 |
Participants are allowed to perform an operant task (click on a mouse) in order to receive a dose drug under investigation (oxycodone dose 0 mg, 15 mg, or 30 mg). The drug breakpoint is the maximum number of responses (mouse clicks) the participant was willing to make to receive the drug. Within the context of abuse liability studies, larger breakpoints represent greater abuse potential of a drug.
| Clicks on a computer mouse | MN-166 + Oxy 0 mg | MN-166 + Oxy 15 mg | MN-166 + Oxy 30 mg | Placebo + Oxy 0 mg | Placebo + Oxy 15 mg | Placebo + Oxy 30 mg |
|---|---|---|---|---|---|---|
| Drug Self-administration Breakpoint | 347 ± 360 | 363 ± 180 | 1472 ± 763 | 43 ± 25 | 1650 ± 948 | 2459 ± 1184 |
Participants are shown a 100-mm line and asked to indicate on that line the extent to which they agree with the descriptor of the drug effect such as "Liking/Liked the Drug." On this visual analog scale participants were instructed that the Left/ 0 mm point on the line represents "not at all," while the right/100 mm point represents "Extremely."
| units on a scale | MN-166 + Oxy 0 mg | MN-166 + Oxy 15 mg | MN-166 + Oxy 30 mg | Placebo + Oxy 0 mg | Placebo + Oxy 15 mg | Placebo + Oxy 30 mg |
|---|---|---|---|---|---|---|
| Positive Subjective Effects to Oxycodone | .8 ± 5.6 | 10.9 ± 23.9 | 24.2 ± 35.1 | .9 ± 3.4 | 15.5 ± 27.2 | 22.7 ± 36.9 |
15-item shortened form of the McGill Pain Questionnaire (Melzack, 1987) that is used to assess the sensory and affective dimensions of the pain experienced Participants describe their experience of pain by choosing among a series of possible answers (None \[score=1\], Mild \[score=2\], Moderate \[score=3\], or Severe \[score=4\]). They were asked to describe the pain as "Throbbing," "Shooting," "Stabbing," "Sharp," "Cramping," "Gnawing," "Hot-Burning," "Aching," "Heavy," "Tender," "Splitting," "Tired-Exhausting," "Sickening," "Fearful," and "Punishing-Cruel." Scores were added across all 15 items to generate a sum score, which ranged between 15 and 60.
| units on a scale | MN-166 + Oxy 0 mg | MN-166 + Oxy 15 mg | MN-166 + Oxy 30 mg | Placebo Oxy 0 mg | Placebo + Oxy 15 mg | Placebo + Oxy 30 mg |
|---|---|---|---|---|---|---|
| Pain Intensity | 30 ± 3 | 25 ± 1 | 26 ± 2 | 31 ± 2 | 29 ± 2 | 27 ± 2 |
Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| MN-166 (Formerly AV411) | 0/12 (0%) | 0/12 (0%) | 3/12 (25%) |
| Placebo | 0/16 (0%) | 0/16 (0%) | 7/16 (43.8%) |
| Event | MN-166 (Formerly AV411) | Placebo |
|---|---|---|
| InsomniaNervous system disorders | 3/12 | 7/16 |
| GI UpsetGastrointestinal disorders | 2/12 | 4/16 |
| HeadacheNervous system disorders | 0/12 | 2/16 |
| FatigueNervous system disorders | 0/12 | 2/16 |
| DepressionPsychiatric disorders | 1/12 | 0/16 |
| Back AcheNervous system disorders | 0/12 | 1/16 |
This was a within-subjects design, however, these numbers denote participant who began with Active (MN-166) maintenance, and those who began under Placebo maintenance.
| Age, Continuous(years) | MN-166 (Formerly AV411) | Placebo | Total |
|---|---|---|---|
| Mean | 41.3 ± 10.8 | 49.5 ± 1.7 | 42.2 ± 8.7 |
| Sex: Female, Male(Participants) | MN-166 (Formerly AV411) | Placebo | Total |
|---|---|---|---|
| Female | 0 | 1 | 1 |
| Male | 3 | 7 | 10 |
| Region of Enrollment(participants) | MN-166 (Formerly AV411) | Placebo | Total |
|---|---|---|---|
| United States | 3 | 8 | 11 |
Plan to share: Yes — Data will be presented at conferences and published in peer-reviewed journals.
This study is completed, as verified in Jul 2017. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
New York State Psychiatric Institute