Opioid-Related DisordersPhase 2AV411NCT00723177
Phase IIa Study of AV411, a Glial Activation Inhibitor, for Opioid Withdrawal
A Phase 2 study testing AV411 in people with Opioid-Related Disorders, run by New York State Psychiatric Institute at 1 site in United States.
Trial summary
Repeated use and/or abuse of opioid medications is generally associated with a characteristic withdrawal syndrome that develops after cessation of drug administration. The present study is designed to evaluate the effectiveness of AV411 to alter opioid-induced withdrawal symptoms. Read more about this study
- Who is it for?
- Ages 21 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Opioid-Related Disorders
- What is being tested?
- AV411
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2008to Jun 2012
- Phase
- Phase 2
- 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 21 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Adults between the ages of 21 and 45
- Current dependence on heroin according to (Diagnostic and Statistical Manual) DSM-IV criteria
- Non-treatment seeking
Who cannot join
- Female participants who are currently pregnant or breastfeeding. Lack of effective birth control 10 days before Study Day 1 (15 days prior to the first PET scan)
- Self-reported use of methadone, buprenorphine, or levo-alpha-acetylmethadol (LAAM) in the past 14 days
- Participants who have a positive history of neurological illness (including epilepsy) or those who have received anti-convulsant therapy during the past 5 years
- Liver disease requiring medication or medical treatment, and/or aspartate or alanine aminotransferase levels greater than 3 times the upper limit of normal
- Gastrointestinal or renal disease that would significantly impair absorption, metabolism or excretion of study drug, or require medication or medical treatment
- Neurological or psychiatric disorders including psychosis, bipolar disorder, organic brain disease, any seizure history or other disorders that require treatment or that could make study compliance difficult
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- Positive tuberculosis (PPD) TB skin test along with a clinical history and chest X-ray indicative of active tuberculosis. (Individuals who have a positive PPD test and have a negative chest X-ray, are not symptomatic for tuberculosis, and do not require anti-tuberculosis therapy will be eligible to participate. Participants will be asked if they ever tested positive for tuberculosis. If so, they will not be given a PPD and a chest X-ray and clinical history will be used for evaluation purposes).
- Presence or positive history of severe medical illness or any cardiovascular disease or heart abnormality, such as low hemoglobin (Hb < 13 g/dL in males, Hb < 11 g/dL in females), or BP > 150/90.
- Requirement for any of the following medications (current or within the past 4 weeks): psychotropics (including sedative/hypnotics, antidepressants, neuroleptics), anticonvulsants, antihypertensives, antiarrhythmics, or antiretroviral medications,. Participants on any current psychoactive prescription medications will be excluded.
- Current dependence (by DSM-IV criteria) on methadone, LAAM, or buprenorphine
- Participants for whom detoxification is not "clinically recommended" such as those with a significant history of overdose following detoxification
- Participation in an investigational drug study within the past 3 months
- Hypersensitivity to any of the medications used in this study
- Participants who are positive for HIV or chronic active hepatitis
- Metal implants or paramagnetic objects contained within the body which may interfere with the MRI scan, as determined in consultation with a neuroradiologist and according to the guidelines set forth in the following reference book commonly used by neuroradiologists: "Guide to MR procedures and metallic objects" Shellock Frank G., Lippincott Williams \& Wilkins Healthcare, Philadelphia, 2001.
- Lifetime exposure to radiation in the workplace, or participation in nuclear medicine procedures, including research protocols, in the past year
- Positive Allen Test indicating lack of collateral blood flow to hand
- History of Reynaud's syndrome
Trial locations and contacts
1 site in 1 country.
United States1 site
New York State Psychiatric Institute/Columbia University
New York, New York, 10032
About this study
Official title: The Safety, Tolerability and Preliminary Efficacy of AV411, a Glial Activation Inhibitor, in Heroin Abusers Under Conditions of Morphine Maintenance and Withdrawal
Repeated use and/or abuse of opioid medications is generally associated with a characteristic withdrawal syndrome that develops after cessation of drug administration. The present study is designed to evaluate the effectiveness of AV411 to alter opioid-induced withdrawal symptoms.
Read the detailed description
Opioid-induced cytokine release and glial activation has been proposed to directly contribute to the affective and physiological aspects of withdrawal. Furthermore, cytokine release following opioid administration has been hypothesized to be a limiting factor in both the duration and magnitude of opioid-induced analgesia. The two primary goals of our study are to assess AV411's ability to 1) reduce the opioid-withdrawal syndrome and 2) increase and prolong the analgesic effects of the mu-opioid agonist, oxycodone. To explore whether AV411 decreases opioid-induced glial cell activation, some participants assigned to the placebo and high dose AV411 groups (n = 6 for each dose condition) will be studied twice with [11C]PK11195, a positron emission tomography (PET) radiotracer used to measure the peripheral benzodiazepine receptor (PBR) in the human brain. The PBR is a receptor located on the mitochondria of the microglia and can be used to examine microglial activation in various brain regions.
- Conditions
- Opioid-Related Disorders
- Being tested
- AV411, Placebo (PCB)
- Keywords
- opioid withdrawal, analgesia
- Medical subject headings
- Opioid-Related Disorders, Agnosia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AV411Drug
Also called ibudilast
Low (20 mg), and high dose (40 mg) of AV411 will be administered orally twice a day (BID) for two consecutive weeks
Placebo (PCB)Drug
Also called PCB or 0 mg
Placebo drug will be administered orally twice a day (BID) for two consecutive weeks
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | This group will receive placebo drug Receives: Drug: Placebo (PCB) |
| Low-dose AV411 | Experimental | This group will receive a low dose of AV411 Receives: Drug: AV411 |
| High-dose AV411 | Experimental | This group will receive a high dose of AV411 Receives: Drug: AV411 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Subjective Opioid Withdrawal Scale Score (SOWS)
Measures severity of opioid withdrawal in opioid dependent populations (0-64). Larger values indicate more severe withdrawal.
Measured: Measured at the end of each two-week maintenance period (i.e., Placebo, Low AV411, High AV411).
Secondary outcomes (1)
The Effects of AV411 on the Analgesic Effects of Oxycodone.
The McGill Pain Questionnaire (Melzack, 1987) was used to assess pain experience immediately following the immersion of the hand in 4 degree Celsius water. Scores were added across all 15 items to generate a sum score, which ranged between 15 and 60. Larger scores indicate greater pain levels.
Measured: Measured at the end of each AV411 of the three two-week maintenance periods
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jul 2008 (estimated)
- Study startOct 2008
- Primary completionApr 2010
- Study completionJun 2012
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.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Opioid-Related DisordersStudies 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
- Phase 2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- New York State Psychiatric Institute
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Responsible party
- Sponsor
- Investigators
- Sandra D Comer, PhD, Principal investigator, New York State Psychiatric Institute and Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00723177
- Sponsor's protocol ID
- #5725
- Other IDs
- P50DA009236
- Acronym
- AV411
- Status last verified
- Oct 2016
- First submitted
- 24 Jul 2008
- Last updated
- 5 Dec 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: Data have been published in a peer-reviewed journal.
Publications
Cooper ZD, Johnson KW, Pavlicova M, Glass A, Vosburg SK, Sullivan MA, Manubay JM, Martinez DM, Jones JD, Saccone PA, Comer SD. The effects of ibudilast, a glial activation inhibitor, on opioid withdrawal symptoms in opioid-dependent volunteers. Addict Biol. 2016 Jul;21(4):895-903. doi: 10.1111/adb.12261. Epub 2015 May 14.
PubMed 25975386Jacobsen JH, Watkins LR, Hutchinson MR. Discovery of a novel site of opioid action at the innate immune pattern-recognition receptor TLR4 and its role in addiction. Int Rev Neurobiol. 2014;118:129-63. doi: 10.1016/B978-0-12-801284-0.00006-3.
PubMed 25175864
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Safety, Tolerability and Preliminary Efficacy of AV411, a Glial Activation Inhibitor, in Heroin Abusers Under Conditions of Morphine Maintenance and Withdrawal
- ClinicalTrials.gov ID
- NCT00723177
- Acronym / sponsor ID
- AV411 / #5725
- Conditions
- Opioid-Related Disorders
- Keywords
- opioid withdrawal, analgesia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- New York State Psychiatric InstituteUniversity, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Study start
- Oct 2008
- Primary completion
- Apr 2010 (actual)
- Study completion
- Jun 2012 (actual)
- First posted
- 28 Jul 2008 (estimated)
- Results
- Posted 5 Dec 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Repeated use and/or abuse of opioid medications is generally associated with a characteristic withdrawal syndrome that develops after cessation of drug administration. The present study is designed to evaluate the effectiveness of AV411 to alter opioid-induced withdrawal symptoms.
Detailed description
Opioid-induced cytokine release and glial activation has been proposed to directly contribute to the affective and physiological aspects of withdrawal. Furthermore, cytokine release following opioid administration has been hypothesized to be a limiting factor in both the duration and magnitude of opioid-induced analgesia. The two primary goals of our study are to assess AV411's ability to 1) reduce the opioid-withdrawal syndrome and 2) increase and prolong the analgesic effects of the mu-opioid agonist, oxycodone. To explore whether AV411 decreases opioid-induced glial cell activation, some participants assigned to the placebo and high dose AV411 groups (n = 6 for each dose condition) will be studied twice with [11C]PK11195, a positron emission tomography (PET) radiotracer used to measure the peripheral benzodiazepine receptor (PBR) in the human brain. The PBR is a receptor located on the mitochondria of the microglia and can be used to examine microglial activation in various brain regions.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: Placebo (PCB)This group will receive placebo drug |
| Low-dose AV411 | Experimental | Drug: AV411This group will receive a low dose of AV411 |
| High-dose AV411 | Experimental | Drug: AV411This group will receive a high dose of AV411 |
Who may qualify
- Ages
- 21 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Adults between the ages of 21 and 45
- Current dependence on heroin according to (Diagnostic and Statistical Manual) DSM-IV criteria
- Non-treatment seeking
Key exclusion criteria (18 listed)
- Female participants who are currently pregnant or breastfeeding. Lack of effective birth control 10 days before Study Day 1 (15 days prior to the first PET scan)
- Self-reported use of methadone, buprenorphine, or levo-alpha-acetylmethadol (LAAM) in the past 14 days
- Participants who have a positive history of neurological illness (including epilepsy) or those who have received anti-convulsant therapy during the past 5 years
- Liver disease requiring medication or medical treatment, and/or aspartate or alanine aminotransferase levels greater than 3 times the upper limit of normal
- Gastrointestinal or renal disease that would significantly impair absorption, metabolism or excretion of study drug, or require medication or medical treatment
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 |
|---|---|---|
| AV411Also: ibudilastLow (20 mg), and high dose (40 mg) of AV411 will be administered orally twice a day (BID) for two consecutive weeks | Drug | High-dose AV411, Low-dose AV411 |
| Placebo (PCB)Also: PCB or 0 mgPlacebo drug will be administered orally twice a day (BID) for two consecutive weeks | Drug | Placebo |
Primary outcome
Subjective Opioid Withdrawal Scale Score (SOWS)
Time frame: Measured at the end of each two-week maintenance period (i.e., Placebo, Low AV411, High AV411).
Measures severity of opioid withdrawal in opioid dependent populations (0-64). Larger values indicate more severe withdrawal.
1 secondary outcome
The Effects of AV411 on the Analgesic Effects of Oxycodone.
Time frame: Measured at the end of each AV411 of the three two-week maintenance periods
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Dec 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 25975386Cooper ZD, Johnson KW, Pavlicova M, Glass A, Vosburg SK, Sullivan MA, Manubay JM, Martinez DM, Jones JD, Saccone PA, Comer SD. The effects of ibudilast, a glial activation inhibitor, on opioid withdrawal symptoms in opioid-dependent volunteers. Addict Biol. 2016 Jul;21(4):895-903. doi: 10.1111/adb.12261. Epub 2015 May 14.
- Derived from this study: PubMed 25175864Jacobsen JH, Watkins LR, Hutchinson MR. Discovery of a novel site of opioid action at the innate immune pattern-recognition receptor TLR4 and its role in addiction. Int Rev Neurobiol. 2014;118:129-63. doi: 10.1016/B978-0-12-801284-0.00006-3.
- Individual participant dataSharing planned: Yes. Data have been published in a peer-reviewed journal.
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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.
Sandra D Comer, PhD principal investigator
New York State Psychiatric Institute and Columbia University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing AV411 in people with Opioid-Related Disorders, run by New York State Psychiatric Institute 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 18 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 5 Dec 2016. 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 5 Dec 2016). 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?
Subjective Opioid Withdrawal Scale Score (SOWS) (time frame: Measured at the end of each two-week maintenance period (i.e., Placebo, Low AV411, High AV411).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00723177, which also lists 2 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 Dec 2016.