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

Sponsor

National Institute on Drug Abuse (NIDA) (NIH)

Overall Status

Recruiting

CT.gov ID

NCT03745339

Collaborator

(none)

150

Enrollment

Location

63.8

Anticipated Duration (Months)

2.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Background:

People with addictions often find it hard to choose the long-term benefits of abstinence over the short-term effects of using drugs. Researchers think this is partly due to parts of the brain involved in certain types of learning and decision-making. Researchers want to test these basic functions using a simple task with pictures and odors.

Objective:

To see if performance in a learning task differs between people who have opioid-use disorder and people who don t.

Eligibility:

Adults 21-60 years old who are willing to fast for at least 6 hours and smell food odors. Those with an opioid-use disorder must either not use for at least 3 weeks or be in treatment.

Design:

Participants will have 1 visit that will take up to 5 hours.

Before the visit, participants will be asked to not eat or drink anything except water for at least 6 hours.

At the visit, participants will be checked for signs of intoxication.

Participants will give urine and breath samples.

Participants will have tests of learning and behavior. They will look at shapes on a computer screen. The shapes will be paired with different food odors.

The odors will come from a sterile tube placed under the nose.

Participants will have their breathing monitored with a belt around the upper abdomen.

About 30 days and 60 days later, participants will be called and asked about their drug use over the past 30 days.

...

Condition or Disease	Intervention/Treatment	Phase
Opioid-Related Disorders Drug Addiction

Detailed Description

Background. People with substance-use disorders may have difficulty guiding their behavior on the basis of not-yet-experienced outcomes such as long-term effects of substance use. Use of mental inferences about future outcomes can be tested in a relatively simple laboratory task called sensory preconditioning.

Objective. To test whether sensory-preconditioning performance is worse in people with opioid use disorder (OUD) than in healthy, demographically matched controls. To increase generalizability, we will examine OUD participants who are in agonist treatment (abstinent or not) and OUD participants who are abstinent but not in treatment. We do not have a hypothesis about differences between those two groups, but we hypothesize that among agonist-treated OUD participants, performance will correlate with degree of abstinence.

Participant population. We will enroll 3 groups of men and women: (1) history of OUD, but abstinent for at least 3 weeks and not in agonist treatment, (2) OUD being treated with an agonist (buprenorphine or methadone), (3) no history of a substance-use disorder (except nicotine, for matching purposes) and not using any drug for nonmedical purposes.

Experimental design. Between-groups cross-sectional single-session laboratory study, with telephone follow-up at 30 and 60 days.

Methods. Each participant will participate in a sensory preconditioning task conducted in a single session. The task uses food odors delivered via nasal cannula and paired with visual cues on a computer screen. There are three phases: (1) Preconditioning, in which 2 pairs of visual cues (A+B, C+D) are shown on the computer screen; participants should acquire automatic associations between A+B and between C+D. (2) Conditioning, in which participants learn associations between the second cue of each pair (B and D) and either a sweet odor (B1), a savory odor (B2), or no odor (D); and (3) Probe Test, in which participants predict whether a visual cue will be paired with the sweet odor, the savory odor, or no odor, by pressing a left, middle, or right button. No odors are actually delivered in the probe test. The test of inference-guided behavior is the ability to associate visual cues A and C with an odor despite their never having been directly paired with an odor. In telephone follow-up at 30 and 60 days, participants will be asked to report drug use and associated problems since the session or follow-up call.

Primary outcome measures. (1) Value-based outcome inference as measured using responding to cues A minus C in the probe test. It is defined as the percentage of trials in which behavioral responses indicate a prediction of any odorant (sweet or savory), independent of whether this prediction is correct. Responding to cues B minus D will be used as a covariate to control for differences in olfactory acuity and non-inference-based task performance.

Secondary outcome measures. (1) The percentage of trials in which the odor prediction is correct. (2) Response latency per cue type. (3) Amplitude and (4) latency of respiratory (sniff) responses per cue type. (5) Acquisition (% responding to B minus D in the last run of conditioning) during the training portion of the inferencing task. (6) Drug use and associated problems at follow-up.

Study Design

Study Type:

Observational

Anticipated Enrollment :

150 participants

Observational Model:

Case-Control

Time Perspective:

Cross-Sectional

Official Title:

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

Actual Study Start Date :

Jun 7, 2019

Anticipated Primary Completion Date :

Apr 1, 2024

Anticipated Study Completion Date :

Oct 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Abstinent OUD Men and women with history of OUD, but abstinent for at least 3 weeks and not in agonist treatment
Controls Men and women with no history of a substance-use disorder (except nicotine, for matching purposes) and not using any drug for nonmedical purposes
In-treatment OUD Men and women with opioid use disorder (OUD) being treated with an agonist (buprenorphine or methadone)

Outcome Measures

Primary Outcome Measures

Outcome inferencing in the probe test [During task]
Percentage of trials with cues A and C in which the participant predicts any odor (sweet or savory), regardless of whether the prediction is correct.

Secondary Outcome Measures

Percentage of trials in which the odor prediction is correct. [During task]
Task-performance measure of secondary interest
Response latency per cue type [During task]
Task-performance measure of secondary interest
Amplitude of respiratory (sniff) responses per cue type [During task]
Task-performance measure of secondary interest
Latency of respiratory (sniff) responses per cue type [During task]
Task-performance measure of secondary interest
Drug use at follow-up [30 and 60 days]
Clinical-outcome measure

Eligibility Criteria

Criteria

Ages Eligible for Study:

21 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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

Control Group
Age between 21 and 60 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.
Abstinent OUD group
Age between 21 and 60 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.
History of opioid-use disorder (DSM-5), to be assessed via the Mini International Neuropsychiatric Interview (MINI). 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 drughistory measures will enable us to examine relationships between those things and inferencing performance.
In-treatment OUD group
Age between 21 and 60 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.
Current enrollment in treatment for OUD with buprenorphine or methadone. 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:

Control Group only

-- History of a substance-use disorder (except nicotine, for matching purposes), or current use of any drug for nonmedical purposes

Control Group and Abstinent Group
Anosmia, dysosmia, or hyposmia (poor olfactory function), to be assessed via Sniffin

Sticks threshold test <4 or via Sniffin Sticks odor identification test <10; or presence of a known smell, taste or ear-nose-throat disorder, to be assessed by history and physical.

History of 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. To be assessed by history and physical. Rationale: any of these could impair task performance.
History of traumatic brain injury (TBI) or major head trauma with sustained loss of consciousness (>30 min). To be assessed by history and physical. Rationale: could impair task performance.
History of neurosurgery, ear/nose/throat (ENT) surgery (including laryngectomies, tracheotomies), or cardiac surgery (including pacemaker or neurostimulator placement). To be assessed by history and physical. Rationale: could impair task performance.
Current use of medications that may impact olfaction including macrolides, antimycotics, fluoroquinolones, ACE inhibitors, protein kinase inhibitors, proton pump inhibitors, and intranasal zinc products. To be assessed by history and physical. Rationale: could impair task performance.
History of endocrine disorders, including hypothyroidism, hypoadrenalism, and diabetes mellitus; significant medical illness including cardiovascular disease, cancer, chronic obstructive pulmonary disease, asthma, renal insufficiency requiring dialysis, etc. To be assessed by history and physical. Rationale: could impair task performance.
History of DSM-5 major psychiatric disorder including uncontrolled major affective disorder, obsessive-compulsive disorder, schizophrenia, and PTSD. (Candidates will not be excluded for a history of depression that is now being successfully treated.) To be assessed by MINI interview. Rationale: could impair task performance.
History of significant food or non-food allergy, including latex, detergents, soaps. To be assessed by history and physical. Rationale: could make odorant exposure risky.
Current sinusitis or allergic, acute, or toxic rhinitis or current nasal polyps or tumors. To be assessed by history and physical. Rationale: could impair task performance
Current use of medications that affect alertness (e.g. barbiturates, benzodiazepines, cannabinoids, chloral hydrate, haloperidol, lithium, carbamazepine, phenytoin, etc.)To be assessed by history and physical. 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.
Cognitive impairment severe enough to preclude informed consent or valid self-report (per History & Physical and Evaluation to Sign Consent).
Urine positive for any illicit drug. Rationale: Controls should have no drug use; 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. In-treatment OUD participants may test positive during screening because they may have ongoing use.
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). 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.
In-treatment OUD group
Anosmia, dysosmia, or hyposmia (poor olfactory function), to be assessed via Sniffin Sticks threshold test <4 or via Sniffin Sticks odor identification test <10; or presence of a known smell, taste or ear-nose-throat disorder, to be assessed by history and physical.
History of 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. To be assessed by history and physical. Rationale: any of these could impair task performance.
History of traumatic brain injury (TBI) or major head trauma with sustained loss of consciousness (>30 min). To be assessed by history and physical. Rationale: could impair task performance.
History of neurosurgery, ear/nose/throat (ENT) surgery (including laryngectomies, tracheotomies), or cardiac surgery (including pacemaker or neurostimulator placement). To be assessed by history and physical. Rationale: could impair task performance.
Current use of medications that may impact olfaction including macrolides, antimycotics, fluoroquinolones, ACE inhibitors, protein kinase inhibitors, proton pump inhibitors, and intranasal zinc products. To be assessed by history and physical. Rationale: could impair task performance.
History of endocrine disorders, including hypothyroidism, hypoadrenalism, and diabetes mellitus; significant medical illness including cardiovascular disease, cancer, chronic obstructive pulmonary disease, asthma, renal insufficiency requiring dialysis, etc. To be assessed by history and physical. Rationale: could impair task performance.
History of DSM-5 major psychiatric disorder including uncontrolled major affective disorder, obsessive-compulsive disorder, schizophrenia, and PTSD. (Candidates will not be excluded for a history of depression that is now being successfully treated.) To be assessed by MINI interview. Rationale: could impair task performance.
History of significant food or non-food allergy, including latex, detergents, soaps. To be assessed by history and physical. Rationale: could make odorant exposure risky.
Current sinusitis or allergic, acute, or toxic rhinitis or current nasal polyps or tumors. To be assessed by history and physical. Rationale: could impair task performance.
Current use of medications that affect alertness (e.g. barbiturates, benzodiazepines, cannabinoids, chloral hydrate, haloperidol, lithium, carbamazepine, phenytoin, etc.) To be assessed by history and physical. 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.
Cognitive impairment severe enough to preclude informed consent or valid self-report (per History & Physical and Evaluation to Sign Consent).