Examining learning differences in people with opioid-use disorder

Outcome Inference in the Sensory Preconditioning Task in Opioid-use Disorder

This study is trying to see how people with a history of opioid-use disorder learn differently compared to healthy individuals by testing their responses to food smells.

Quick facts

• Study type: Observational
• Enrollment: 150 (estimated)
• Ages: 21 Years to 60 Years
• Sex: All
• Sponsor: National Institutes of Health Clinical Center (CC) (NIH)
• Locations: 1 site (Baltimore, Maryland)
• Trial ID: NCT03745339 on ClinicalTrials.gov

What this trial studies

This observational study aims to investigate how individuals with opioid-use disorder (OUD) perform on a sensory preconditioning task compared to healthy controls. Participants will be divided into three groups: those with a history of OUD who are abstinent, those undergoing agonist treatment, and healthy individuals without substance use disorders. The study will involve a single visit lasting up to 5 hours, during which participants will undergo a task involving food odors and provide urine and breath samples. The goal is to understand the relationship between learning performance and abstinence in OUD patients.

Who should consider this trial

Good fit: Ideal candidates include adults aged 21-65 with a history of opioid-use disorder who are either abstinent for at least 3 weeks or currently in agonist treatment.

Not a fit: Patients who are not willing to fast for 6 hours or those with active substance use disorders other than opioids may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could enhance understanding of decision-making processes in individuals with opioid-use disorder, potentially leading to improved treatment strategies.

How similar studies have performed: While this approach is novel in its specific application to opioid-use disorder, similar studies have shown promise in understanding learning and decision-making in addiction.

Eligibility criteria

* INCLUSION CRITERIA:

The enrollment target for the protocol is 120 (40 healthy controls, 40 patients on agonist maintenance, and 40 participants who have met DSM 5 criteria for OUD, but are now abstinent (for at least 3 weeks) and not on agonist maintenance.

All Participants

* Age between 21 and 65 years inclusive. Rationale: objective olfactory impairment grows more prevalent with age; after age 53, the prevalence is 24.5%, increasing to 62.5 % in people aged 80-97 years.
* Willing to fast for at least 6 hours prior to the study session and be exposed to food odors. These will be assessed with the "019 Additional History Form" questionnaire.

Additional Criteria for Abstinent OUD group

* History of opioid-use disorder (DSM-5), to be assessed via the Mini International Neuropsychiatric Interview (MINI) or the Structured Clinical Interview for DSM-5 (SCID). History of SUDs can include substances in addition to opioids (e.g., cocaine).
* Abstinent \> 3 weeks from all illicit substances (tobacco smoking and nondependent drinking permissible), to be assessed via 30-day timeline follow-back calendar. (Current abstinence will be confirmed via urine screen: see exclusion criteria.) Rationale: Although heterogeneity will be considerable, what all enrollees will have in common is having become abstinent from opioids long enough to be past withdrawal symptoms. Their heterogeneity in duration of abstinence and other drug-history measures will enable us to examine relationships between those things and inferencing performance.

Additional Criteria for In-treatment OUD group

-Current enrollment in treatment for OUD with buprenorphine or methadone (\>3 weeks on stable dose). Current use of illicit substances during treatment is permissible but not required. Rationale: Again, heterogeneity will be considerable, but what all enrollees will have in common is having sought treatment for their OUD and being currently maintained on an agonist that permits adaptive everyday functioning. Their heterogeneity in ongoing use of illicit substances will enable us to examine relationships between inferencing performance and treatment response.

EXCLUSION CRITERIA:

All participants

* Anosmia, dysosmia, or hyposmia (poor olfactory function), to be assessed via Sniffin Sticks threshold test \<4 or via Sniffin Sticks odor identification test \<10.
* History of any neurological condition resulting in inability to perform study task. Examples include but not limited to degenerative processes of the CNS (Parkinson disease, Alzheimer disease); other neurologic diseases (Huntington disease, multiple sclerosis, other motor-neuron diseases); inflammatory conditions (sarcoidosis, Wegener granulomatosis); or significant cerebrovascular disease including (but not limited to) epilepsy, stroke, or meningitis; traumatic brain injury (TBI) or major head trauma with sustained loss of consciousness (\>30 min). To be assessed by history and physical and evaluation to sign screening consent. Eligibility will be determined based on MAI review of participants ability to perform study task. MAI will consider but is not limited to H and P results for mental status exam, language exam, and attention span exam. Rationale: any of these could impair task performance.
* History of current (past 12 months) uncontrolled DSM-5 major psychiatric disorder including major affective disorder, obsessive-compulsive disorder, schizophrenia, and PTSD. (Candidates will not be excluded for a history of major psychiatric disorder that is now being successfully treated.) To be assessed by MINI or SCID interview. Rationale: could impair task performance.
* History of anaphylaxis due to, e.g., significant asthma, food or non-food allergy, or intolerance to odors (including latex, detergents, soaps, etc.). To be assessed by history and physical. Rationale: could make odorant exposure risky.
* Current use of medications or substances that affect alertness and that cannot be withheld on the morning of the study visit (e.g., barbiturates, benzodiazepines, cannabinoids, chloral hydrate, haloperidol, lithium, carbamazepine, phenytoin, etc.). To be assessed by history and physical. Whether candidate will be requested to withhold any medication will be determined based on MAI judgment. Additionally, if participant has a BrAC \>0.08, MAI will use clinical judgement to determine if participant should be rescheduled. Rationale: could impair task performance.
* For women: pregnancy. To be assessed by history and physical and by urine testing. Rationale: Could affect task performance-physiological and hormonal changes during pregnancy influence rhinological function.
* Any other medical illness or condition that in the judgment of the investigators is incompatible with study participation.

Additional criteria for Control Group

* History of a substance-use disorder (except nicotine, for matching purposes), or current use of any drug for nonmedical purposes. Controls, who cannot have a history of OUD, will be assessed by their medical history and physical examination for the presence of any signs or symptoms consistent with opioid withdrawal. Any Control with any sign or symptom consistent with opioid withdrawal will be evaluated by the MAI to rule out opioid withdrawal if possible.
* Urine positive for any illicit drug. Rationale: Controls should have no drug use. A UDS that is positive for a prescribed medication that the MAI has determined is not due to illicit drug use will not be exclusionary.

Additional criteria for Abstinent Group

* Urine positive for any illicit drug. Rationale: Abstinent OUD group should have no drug use in the last 3 weeks which would include the several-day time frame to which urine screens are sensitive. A UDS that is positive for a prescribed medication that the MAI has determined is not due to illicit drug use will not be exclusionary.
* Current signs or symptoms of opioid withdrawal. These will be assessed in the Abstinent group via the Clinical Opioid Withdrawal Scale (COWS) and the Subjective Opioid Withdrawal Scale (SOWS).

Additional criteria for In-treatment OUD group

-Urine negative for opioid agonist that the participant is taking as part of their OUD treatment. Rationale: In-treatment OUD group should be in treatment. A negative test suggests the participant is not adhering to their treatment plan. In-treatment OUD participants may test positive for other substances as well as their opioid agonist because they may have ongoing illicit drug use.

Where this trial is running

Baltimore, Maryland

• National Institute on Drug Abuse — Baltimore, Maryland, United States (Recruiting)

Study contacts

• Principal investigator: Thorsten Kahnt, Ph.D. — National Institute on Drug Abuse (NIDA)
• Study coordinator: NIDA IRP Screening Team

Conditions Opioid-Related Disorders; Drug Addiction; Addiction; Orbitofrontal Cortex; Associative Learning; Implicit Learning; Natural History