Opioid Use DisorderNCT06800703
Opioid Use Disorder and Pain
An observational study of Opioid Use Disorder and Healthy Controls Group - Age and Sex-matched, run by Yale University at 1 site in United States.
Trial summary
The goal of this observational study is to characterize the brain processes of pain avoidance learning dysfunctions in individuals with opioid use disorder (OUD). The main questions it aims to answer are: Compared with healthy controls, do those with OUD exhibit impaired avoidance learning in response to pain? What… Read more about this study
- Who is it for?
- Ages 21 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Opioid Use Disorder, Healthy Controls Group - Age and Sex-matched
- What is being tested?
- follow up interviews for 12 months to determine opioid use
- Type of treatment
- Lifestyle or therapy programme
- How many people
- 180 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Feb 2025to Jan 2028
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Study population: Treatment-seeking OUD patients will be recruited from local clinics. Those with OUD not seeking treatment and healthy controls will be recruited from New Haven and surrounding areas in Connecticut.
Who may be able to join
None listed.
Who cannot join
- Any significant current medical condition such as neurological, cardiovascular, endocrine, renal, hepatic, thyroid pathology.
- History of head injury with loss of consciousness (> 30 minutes).
- Current or past DSM-IV or DSM 5 diagnosis of a major psychiatric disorder (other than opioid and nicotine use disorders) that required hospitalization, or that required daily medications for over 4 weeks. Such medications include antidepressants, anticholinergics, antipsychotics, anxiolytics, lithium, psychotropic drugs not otherwise specified including herbal products, drugs with psychomotor effects or with anxiolytics, stimulant, or antipsychotic properties, any other psychoactive drugs, and sedatives/hypnotics. Individuals with current depressive or anxiety symptoms requiring treatment or currently being treated for these symptoms will be excluded.
- Any subjects with foreign ferromagnetic metal objects in their body or other MR contraindications will be excluded. Individuals who previously worked in metal industry or with metal shavings (due to a risk of any remaining metal particles moving in the eye during the MRI).
- Pregnant or lactating women will not be recruited for the study.
- Cannot or are not willing to lie comfortably flat on his/her back for up to 2 hours in the MRI scanner (self-report).
Show all 64Show fewer
- Body weight > 550 lbs. The MR scanner bed is tested to a weight limit of 550 lbs.
- No pPlans to relocate out of state in the next 12 months (for follow-up purposes).
- Still experiencing significant withdrawal symptoms.
- Individuals with regular opioid use
- To be eligible for inclusion in the study, an individual must meet all of the following criteria:
- Between ages 21-60 years old.
- Able to read and write and provide written informed consent.
- Use non-prescribed opioids on a weekly basis or more.
- Physically healthy with no major medical illnesses, history of head injury or any neurological illness
- No plans to relocate out of state in the next 12 months (for follow-up purposes).
- Speak English
- Any significant current medical condition such as neurological, cardiovascular, endocrine, renal, hepatic, thyroid pathology.
- History of head injury with loss of consciousness (> 30 minutes).
- Current or past DSM-IV or DSM 5 diagnosis of a major psychiatric disorder (other than opioid and nicotine use disorders) that required hospitalization, or that required daily medications for over 4 weeks. Such medications include antidepressants, anticholinergics, antipsychotics, anxiolytics, lithium, psychotropic drugs not otherwise specified including herbal products, drugs with psychomotor effects or with anxiolytics, stimulant, or antipsychotic properties, any other psychoactive drugs, and sedatives/hypnotics. Individuals with current depressive or anxiety symptoms requiring treatment or currently being treated for these symptoms will be excluded.
- Any subjects with foreign ferromagnetic metal objects in their body or other MR contraindications will be excluded.
- Pregnant or lactating women will not be recruited for the study.
- Cannot or are not willing to lie comfortably flat on his/her back for up to 2 hours in the MRI scanner (self-report).
- Body weight > 550 lbs. The MR scanner bed is tested to a weight limit of 550 lbs.
- Individuals with regular opioid use
- To be eligible for inclusion in the study, an individual must meet all of the following criteria:
- Between ages 21-60 years old.
- Able to read and write and provide written informed consent.
- Use non-prescribed opioids on a weekly basis or more.
- Physically healthy with no major medical illnesses, history of head injury or any neurological illness
- No plans to relocate out of state in the next 12 months (for follow-up purposes).
- Speak English
- Any significant current medical condition such as neurological, cardiovascular, endocrine, renal, hepatic, thyroid pathology.
- History of head injury with loss of consciousness (> 30 minutes).
- Current or past DSM-IV or DSM 5 diagnosis of a major psychiatric disorder (other than opioid and nicotine use disorders) that required hospitalization, or that required daily medications for over 4 weeks. Such medications include antidepressants, anticholinergics, antipsychotics, anxiolytics, lithium, psychotropic drugs not otherwise specified including herbal products, drugs with psychomotor effects or with anxiolytics, stimulant, or antipsychotic properties, any other psychoactive drugs, and sedatives/hypnotics. Individuals with current depressive or anxiety symptoms requiring treatment or currently being treated for these symptoms will be excluded.
- Any subjects with foreign ferromagnetic metal objects in their body or other MR contraindications will be excluded.
- Pregnant or lactating women will not be recruited for the study.
- Cannot or are not willing to lie comfortably flat on his/her back for up to 2 hours in the MRI scanner (self-report).
- Body weight > 550 lbs. The MR scanner bed is tested to a weight limit of 550 lbs.
- Individuals with regular opioid use
- To be eligible for inclusion in the study, an individual must meet all of the following criteria:
- Between ages 21-60 years old.
- Able to read and write and provide written informed consent.
- Use non-prescribed opioids on a weekly basis or more.
- Physically healthy with no major medical illnesses, history of head injury or any neurological illness
- No plans to relocate out of state in the next 12 months (for follow-up purposes).
- Speak English
- Any significant current medical condition such as neurological, cardiovascular, endocrine, renal, hepatic, thyroid pathology.
- History of head injury with loss of consciousness (> 30 minutes).
- Current or past DSM-IV or DSM 5 diagnosis of a major psychiatric disorder (other than opioid and nicotine use disorders) that required hospitalization, or that required daily medications for over 4 weeks. Such medications include antidepressants, anticholinergics, antipsychotics, anxiolytics, lithium, psychotropic drugs not otherwise specified including herbal products, drugs with psychomotor effects or with anxiolytics, stimulant, or antipsychotic properties, any other psychoactive drugs, and sedatives/hypnotics. Individuals with current depressive or anxiety symptoms requiring treatment or currently being treated for these symptoms will be excluded.
- Any subjects with foreign ferromagnetic metal objects in their body or other MR contraindications will be excluded.
- Pregnant or lactating women will not be recruited for the study.
- Cannot or are not willing to lie comfortably flat on his/her back for up to 2 hours in the MRI scanner (self-report).
- Body weight > 550 lbs. The MR scanner bed is tested to a weight limit of 550 lbs.
- Healthy controls (HC) Inclusion Criteria
- Between ages 1821-60 years old.
- Able to read and write and provide written informed consent.
- Demographics matching OUD participants.
- Speak English
- Meet criteria for current or history of any Axis I (except nicotine use) disorder.
- Any significant current medical condition such as neurological, cardiovascular, endocrine, renal, hepatic, thyroid pathology. History of head injury with loss of consciousness (> 30 minutes).
- 4. Any subjects with foreign ferromagnetic metal objects in their body or other MR contraindications will be excluded.
- 5. Pregnant or lactating women will not be recruited for the study. 6. Cannot or are not willing to lie comfortably flat on his/her back for up to 2 hours in the MRI scanner (self-report).
- 7. Body weight > 550 lbs. The MR scanner bed is tested to a weight limit of 550 lbs.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Connecticut Mental Health Center, S105
New Haven, Connecticut, 06519
Thang M Le, PhD, 203-974-7360, thang.le@yale.edu
About this study
The goal of this observational study is to characterize the brain processes of pain avoidance learning dysfunctions in individuals with opioid use disorder (OUD). The main questions it aims to answer are:
Compared with healthy controls, do those with OUD exhibit impaired avoidance learning in response to pain? What are the brain processes that are associated with this avoidance learning dysfunction? Do these brain processes serve to predict future use or relapse?
Read more
Researchers will compare those with OUD and healthy controls to determine avoidance learning dysfunction and its relationship with opioid use.
Participants will be performing a learning task inside an fMRI scanner. Those with OUD will also be followed up for a year to determine future opioid use.
Read the detailed description
Opioid Use Disorder (OUD) is a chronic condition with exceptionally high relapse rates. Over 80% of patients receiving treatment relapse within a year. To understand the etiological processes of OUD, investigators have focused on reward seeking as a primary drinking motive. However, whereas reward and sensation seeking may be central to the early stages of OUD, it is posited that drinking as an avoidance coping behavior plays a more critical role in the maintenance of OUD. Specifically, as opioid escalates, consumption is increasingly driven by individuals' enhanced sensitivity to the aversive consequences of withdrawal. This indicates a fundamental shift of motivation from positive to negative reinforcement in OUD. Paradoxically, while users seek opioid to avoid painful physical and emotional states, chronic opioid use heightens pain reactivity, which further motivates drug use as an avoidance coping strategy. Over time, this maladaptive behavior becomes progressively less amenable to cognitive control, trapping users in a spiraling cycle of drug use and distress. The investigators thus hypothesize that dysfunctional avoidance learning is a central pathophysiological process of OUD.
Avoidance learning is a product of pain reactivity and cognitive control and their underlying brain circuits. Yet, how avoidance learning and its circuit processes are compromised in individuals with OUD remains unclear. This study aims to fill this important gap in research by investigating avoidance learning deficits as a principal mechanism of OUD.
The current proposal leverages neuroimaging, physiological recordings, and clinical assessments of avoidance learning to identify a set of markers to distinguish those with OUD from healthy controls (HC), evaluate the "diagnostic" accuracy of these markers, and describe how they may predict relapse. The investigators will also examine reward learning as a contrast to differentiate its role in OUD. Avoidance and reward learning will be operationalized via a probabilistic learning go/no-go task in which participants learn to associate cues with outcomes to avoid electric shocks and optimize reward. First, the investigators will identify brain dysfunctions in avoidance and reward learning in OUD patients and establish their inter-relationships with clinical and drug use characteristics. Next, in addition to continuing recruitment, the investigators will follow up with OUD patients for 12 months to identify predictors of relapse. The investigators will also follow up with opioid regular users to determine changes in opioid use over time.
Individuals with OUD and HCs will be recruited from the Greater New Haven, Hartford, Bridgeport areas of CT. Those with OUD will be drawn by self-referral based on seeing flyers and brochures posted at treatment programs such as the Substance Abuse Treatment Unit (SATU) and the Connecticut Mental Health Center (CMHC), by advertisements of the study, or by word of mouth. HCs will be recruited from the community by flyers and advertisements or by word of mouth.
Ninety treatment-seeking individuals with OUD (45 women) between 21 and 60 years of age and meeting the diagnosis of moderate to severe OUD will be recruited to participate in the study.
Forty individuals with regular opioid use (i.e., at least weekly, non-prescription) (20 women) aged between 21-60 who are not seeking treatment will also be recruited.
Ninety HCs (45 women) with matching demographics (including age, sex, race, and education) will be recruited. HCs will undergo the same intake assessments to confirm eligibility.
- Being tested
- follow up interviews for 12 months to determine opioid use
- Keywords
- opioid use disorder, pain, avoidance learning, prediction
- Medical subject headings
- Opioid-Related Disorders, Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
follow up interviews for 12 months to determine opioid useBehavioural
Follow-up
| Study group | Role | What they receive |
|---|---|---|
| opioid use disorder | individuals with OUD diagnosis Receives: Behavioral: follow up interviews for 12 months to determine opioid use | |
| Healthy controls | Healthy individuals without substance use disorders |
What is being measured
The primary outcome is the main question the study is designed to answer.
Avoidance learning measure
Task performance measure of avoidance learning, quantified by response time and performance accuracy. Those with OUD are expected to have lower performance accuracy, lower learning rates, and higher response time during avoidance learning relative to healthy controls
Measured: Day 1 (immediately after consent and clinical assessment)
opioid use
Quantity of opioid use following the baseline visit, measured by times use per week. Timeline follow back method will be used to assess the quantity of opioid use during the follow-up period. The investigators will examine this opioid use quantity in relation with avoidance learning deficits. The investigators expect greater avoidance dysfunction at baseline to predict higher weekly use of opioids
Measured: During the 12-month follow-up period
Brain activity during avoidance learning
The brain activation magnitude associated with avoidance learning and avoidance learning dysfunction during the task performance. Brain activation will be computed by using contrast between avoidance learning vs. neutral conditions. Contrasts between two subject groups (i.e., OUD vs. HC) will also be examined. The investigators expect OUD patients to exhibit greater activations in the pain circuit during avoidance learning relative to healthy controls. Additionally, pain circuit activation will be assessed in association with opioid use severity during follow-up period.
Measured: Day 1 (immediately after consent and clinical assessment)
Secondary outcomes (3)
Comparison of avoidance learning rate between women and men
Sex differences in avoidance learning dysfunction in those with opioid use disorder. Comparison between women and men will be conducted in relation to their avoidance learning task performance (e.g., performance accuracy, response time)
Measured: Day 1 (immediately after consent and clinical assessment)
Comparison of brain activity during avoidance learning between women and men
Comparison between women and men will be conducted in relation to their brain activations during avoidance learning to determine whether women or men may have higher brain activity amplitude during learning of avoidance behavior.
Measured: Day 1 (immediately after consent and clinical assessment)
Relationship between sex differences in avoidance learning and opioid use
Investigators will examine whether opioid use severity has a relationship with differences in avoidance learning performance.
Measured: Day 1 (immediately after consent and clinical assessment)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2025
- Study start4 Feb 2025
- Primary completionJan 2028 (estimated)
- Study completionJan 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Opioid Use DisorderStudies 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
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 180 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- Responsible party
- Sponsor
- Investigators
- Thang M Le, PhD, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06800703
- Sponsor's protocol ID
- 2000039121
- Other IDs
- 4R00AA029716-03
- Status last verified
- Jun 2026
- First submitted
- 8 Jan 2025
- Last updated
- 16 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: There is no plan to share IPD at this time
Publications
Baker TB, Piper ME, McCarthy DE, Majeskie MR, Fiore MC. Addiction motivation reformulated: an affective processing model of negative reinforcement. Psychol Rev. 2004 Jan;111(1):33-51. doi: 10.1037/0033-295X.111.1.33.
PubMed 14756584Carcoba LM, Contreras AE, Cepeda-Benito A, Meagher MW. Negative affect heightens opiate withdrawal-induced hyperalgesia in heroin dependent individuals. J Addict Dis. 2011 Jul-Sep;30(3):258-70. doi: 10.1080/10550887.2011.581985.
PubMed 21745048Ren ZY, Shi J, Epstein DH, Wang J, Lu L. Abnormal pain response in pain-sensitive opiate addicts after prolonged abstinence predicts increased drug craving. Psychopharmacology (Berl). 2009 Jun;204(3):423-9. doi: 10.1007/s00213-009-1472-0. Epub 2009 Jan 27.
PubMed 19172249Grella CE, Lovinger K. 30-year trajectories of heroin and other drug use among men and women sampled from methadone treatment in California. Drug Alcohol Depend. 2011 Nov 1;118(2-3):251-8. doi: 10.1016/j.drugalcdep.2011.04.004. Epub 2011 May 6.
PubMed 21549528Le TM, Zhornitsky S, Wang W, Zhang S, Li CR. Problem drinking alters gray matter volume and food cue responses of the lateral orbitofrontal cortex. Addict Biol. 2021 Jan;26(1):e12857. doi: 10.1111/adb.12857. Epub 2019 Nov 20.
PubMed 31746092Wang W, Zhornitsky S, Le TM, Zhang S, Li CR. Heart Rate Variability, Cue-Evoked Ventromedial Prefrontal Cortical Response, and Problem Alcohol Use in Adult Drinkers. Biol Psychiatry Cogn Neurosci Neuroimaging. 2020 Jun;5(6):619-628. doi: 10.1016/j.bpsc.2019.12.013. Epub 2019 Dec 30.
PubMed 32061544Le TM, Chao H, Levy I, Li CR. Age-Related Changes in the Neural Processes of Reward-Directed Action and Inhibition of Action. Front Psychol. 2020 Jun 10;11:1121. doi: 10.3389/fpsyg.2020.01121. eCollection 2020.
PubMed 32587547Le TM, Zhang S, Zhornitsky S, Wang W, Li CR. Neural correlates of reward-directed action and inhibition of action. Cortex. 2020 Feb;123:42-56. doi: 10.1016/j.cortex.2019.10.007. Epub 2019 Oct 31.
PubMed 31747630
Study at a glance
From the registry record, last updated by the sponsor on 16 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Opioid Use Disorder and Pain
- ClinicalTrials.gov ID
- NCT06800703
- Acronym / sponsor ID
- 2000039121
- Keywords
- opioid use disorder, pain, avoidance learning, prediction
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 180 participants (estimated)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- Study start
- 4 Feb 2025 (actual)
- Primary completion
- Jan 2028 (estimated)
- Study completion
- Jan 2028 (estimated)
- First posted
- 30 Jan 2025 (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.
The goal of this observational study is to characterize the brain processes of pain avoidance learning dysfunctions in individuals with opioid use disorder (OUD). The main questions it aims to answer are:
Compared with healthy controls, do those with OUD exhibit impaired avoidance learning in response to pain? What are the brain processes that are associated with this avoidance learning dysfunction? Do these brain processes serve to predict future use or relapse?
Researchers will compare those with OUD and healthy controls to determine avoidance learning dysfunction and its relationship with opioid use.
Participants will be performing a learning task inside an fMRI scanner. Those with OUD will also be followed up for a year to determine future opioid use.
Detailed description
Opioid Use Disorder (OUD) is a chronic condition with exceptionally high relapse rates. Over 80% of patients receiving treatment relapse within a year. To understand the etiological processes of OUD, investigators have focused on reward seeking as a primary drinking motive. However, whereas reward and sensation seeking may be central to the early stages of OUD, it is posited that drinking as an avoidance coping behavior plays a more critical role in the maintenance of OUD. Specifically, as opioid escalates, consumption is increasingly driven by individuals' enhanced sensitivity to the aversive consequences of withdrawal. This indicates a fundamental shift of motivation from positive to negative reinforcement in OUD. Paradoxically, while users seek opioid to avoid painful physical and emotional states, chronic opioid use heightens pain reactivity, which further motivates drug use as an avoidance coping strategy. Over time, this maladaptive behavior becomes progressively less amenable to cognitive control, trapping users in a spiraling cycle of drug use and distress. The investigators thus hypothesize that dysfunctional avoidance learning is a central pathophysiological process of OUD.
Avoidance learning is a product of pain reactivity and cognitive control and their underlying brain circuits. Yet, how avoidance learning and its circuit processes are compromised in individuals with OUD remains unclear. This study aims to fill this important gap in research by investigating avoidance learning deficits as a principal mechanism of OUD.
The current proposal leverages neuroimaging, physiological recordings, and clinical assessments of avoidance learning to identify a set of markers to distinguish those with OUD from healthy controls (HC), evaluate the "diagnostic" accuracy of these markers, and describe how they may predict relapse. The investigators will also examine reward learning as a contrast to differentiate its role in OUD. Avoidance and reward learning will be operationalized via a probabilistic learning go/no-go task in which participants learn to associate cues with outcomes to avoid electric shocks and optimize reward. First, the investigators will identify brain dysfunctions in avoidance and reward learning in OUD patients and establish their inter-relationships with clinical and drug use characteristics. Next, in addition to continuing recruitment, the investigators will follow up with OUD patients for 12 months to identify predictors of relapse. The investigators will also follow up with opioid regular users to determine changes in opioid use over time.
Individuals with OUD and HCs will be recruited from the Greater New Haven, Hartford, Bridgeport areas of CT. Those with OUD will be drawn by self-referral based on seeing flyers and brochures posted at treatment programs such as the Substance Abuse Treatment Unit (SATU) and the Connecticut Mental Health Center (CMHC), by advertisements of the study, or by word of mouth. HCs will be recruited from the community by flyers and advertisements or by word of mouth.
Ninety treatment-seeking individuals with OUD (45 women) between 21 and 60 years of age and meeting the diagnosis of moderate to severe OUD will be recruited to participate in the study.
Forty individuals with regular opioid use (i.e., at least weekly, non-prescription) (20 women) aged between 21-60 who are not seeking treatment will also be recruited.
Ninety HCs (45 women) with matching demographics (including age, sex, race, and education) will be recruited. HCs will undergo the same intake assessments to confirm eligibility.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| opioid use disorder | – | Behavioral: follow up interviews for 12 months to determine opioid useindividuals with OUD diagnosis |
| Healthy controls | – | –Healthy individuals without substance use disorders |
Who may qualify
- Ages
- 21 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- Treatment-seeking OUD patients will be recruited from local clinics. Those with OUD not seeking treatment and healthy controls will be recruited from New Haven and surrounding areas in Connecticut.
Key inclusion criteria (0 listed)
Key exclusion criteria (64 listed)
- Any significant current medical condition such as neurological, cardiovascular, endocrine, renal, hepatic, thyroid pathology.
- History of head injury with loss of consciousness (> 30 minutes).
- Current or past DSM-IV or DSM 5 diagnosis of a major psychiatric disorder (other than opioid and nicotine use disorders) that required hospitalization, or that required daily medications for over 4 weeks. Such medications include antidepressants, anticholinergics, antipsychotics, anxiolytics, lithium, psychotropic drugs not otherwise specified including herbal products, drugs with psychomotor effects or with anxiolytics, stimulant, or antipsychotic properties, any other psychoactive drugs, and sedatives/hypnotics. Individuals with current depressive or anxiety symptoms requiring treatment or currently being treated for these symptoms will be excluded.
- Any subjects with foreign ferromagnetic metal objects in their body or other MR contraindications will be excluded. Individuals who previously worked in metal industry or with metal shavings (due to a risk of any remaining metal particles moving in the eye during the MRI).
- Pregnant or lactating women will not be recruited for the study.
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 |
|---|---|---|
| follow up interviews for 12 months to determine opioid useFollow-up | Behavioural | opioid use disorder |
Primary outcome
Avoidance learning measure
Time frame: Day 1 (immediately after consent and clinical assessment)
Task performance measure of avoidance learning, quantified by response time and performance accuracy. Those with OUD are expected to have lower performance accuracy, lower learning rates, and higher response time during avoidance learning relative to healthy controls
opioid use
Time frame: During the 12-month follow-up period
Quantity of opioid use following the baseline visit, measured by times use per week. Timeline follow back method will be used to assess the quantity of opioid use during the follow-up period. The investigators will examine this opioid use quantity in relation with avoidance learning deficits. The investigators expect greater avoidance dysfunction at baseline to predict higher weekly use of opioids
Brain activity during avoidance learning
Time frame: Day 1 (immediately after consent and clinical assessment)
The brain activation magnitude associated with avoidance learning and avoidance learning dysfunction during the task performance. Brain activation will be computed by using contrast between avoidance learning vs. neutral conditions. Contrasts between two subject groups (i.e., OUD vs. HC) will also be examined. The investigators expect OUD patients to exhibit greater activations in the pain circuit during avoidance learning relative to healthy controls. Additionally, pain circuit activation will be assessed in association with opioid use severity during follow-up period.
3 secondary outcomes
Comparison of avoidance learning rate between women and men
Time frame: Day 1 (immediately after consent and clinical assessment)
Comparison of brain activity during avoidance learning between women and men
Time frame: Day 1 (immediately after consent and clinical assessment)
Relationship between sex differences in avoidance learning and opioid use
Time frame: Day 1 (immediately after consent and clinical assessment)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jun 2026.
- Results publication: PubMed 14756584Baker TB, Piper ME, McCarthy DE, Majeskie MR, Fiore MC. Addiction motivation reformulated: an affective processing model of negative reinforcement. Psychol Rev. 2004 Jan;111(1):33-51. doi: 10.1037/0033-295X.111.1.33.
- Results publication: PubMed 21745048Carcoba LM, Contreras AE, Cepeda-Benito A, Meagher MW. Negative affect heightens opiate withdrawal-induced hyperalgesia in heroin dependent individuals. J Addict Dis. 2011 Jul-Sep;30(3):258-70. doi: 10.1080/10550887.2011.581985.
- Results publication: PubMed 19172249Ren ZY, Shi J, Epstein DH, Wang J, Lu L. Abnormal pain response in pain-sensitive opiate addicts after prolonged abstinence predicts increased drug craving. Psychopharmacology (Berl). 2009 Jun;204(3):423-9. doi: 10.1007/s00213-009-1472-0. Epub 2009 Jan 27.
- Results publication: PubMed 21549528Grella CE, Lovinger K. 30-year trajectories of heroin and other drug use among men and women sampled from methadone treatment in California. Drug Alcohol Depend. 2011 Nov 1;118(2-3):251-8. doi: 10.1016/j.drugalcdep.2011.04.004. Epub 2011 May 6.
- Results publication: PubMed 31746092Le TM, Zhornitsky S, Wang W, Zhang S, Li CR. Problem drinking alters gray matter volume and food cue responses of the lateral orbitofrontal cortex. Addict Biol. 2021 Jan;26(1):e12857. doi: 10.1111/adb.12857. Epub 2019 Nov 20.
- Results publication: PubMed 32061544Wang W, Zhornitsky S, Le TM, Zhang S, Li CR. Heart Rate Variability, Cue-Evoked Ventromedial Prefrontal Cortical Response, and Problem Alcohol Use in Adult Drinkers. Biol Psychiatry Cogn Neurosci Neuroimaging. 2020 Jun;5(6):619-628. doi: 10.1016/j.bpsc.2019.12.013. Epub 2019 Dec 30.
- Results publication: PubMed 32587547Le TM, Chao H, Levy I, Li CR. Age-Related Changes in the Neural Processes of Reward-Directed Action and Inhibition of Action. Front Psychol. 2020 Jun 10;11:1121. doi: 10.3389/fpsyg.2020.01121. eCollection 2020.
- Results publication: PubMed 31747630Le TM, Zhang S, Zhornitsky S, Wang W, Li CR. Neural correlates of reward-directed action and inhibition of action. Cortex. 2020 Feb;123:42-56. doi: 10.1016/j.cortex.2019.10.007. Epub 2019 Oct 31.
- Individual participant dataSharing planned: No. There is no plan to share IPD at this time
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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.
Thang M Le, 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?
An observational study of Opioid Use Disorder and Healthy Controls Group - Age and Sex-matched, 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 0 inclusion and 64 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: looking for participants now, as of the sponsor's last update on 16 Jun 2026. 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.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Thang M Le, PhD (203-974-7360, thang.le@yale.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Avoidance learning measure (time frame: Day 1 (immediately after consent and clinical assessment)). The study lists 3 primary outcomes in all. 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 NCT06800703, which also lists 8 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 16 Jun 2026; AzTrials last refreshed its copy on 31 Oct 2026.