Project 1 Aim 2, Adaptations of the Brain in Chronic Pain With Opioid Exposure

NCT ID: NCT05463367

Last Updated: 2024-11-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-01-01

Study Completion Date

2025-06-01

Brief Summary

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This study is designed to track brain functional changes in individuals with i) chronic back pain + opioid use (CBP+O) and individuals with ii) chronic back pain + opioid misuse disorder (CBP+mOUD) following a brief drug delay and re-exposure manipulation. Re-exposure could be placebo, the participant's own opioid dose, or a dopaminergic treatment (DA+NSAID). The participants will be also evaluated for changes in cognition, emotion, and motor abilities with opioid delay and re-exposure to placebo, opioid, or DA+NSAID.

Detailed Description

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Screening Visit (2-3 hours) (if applicable):

Participants that have participated in Project 1 Aim 1 within three months of consenting to Project 1 Aim 2 will not require a screening visit and can continue on to Visit 1, 2 and 3 of Aim 2.

A screening visit will be applicable for those participants that did not participate in Project 1 Aim 1, and for those that had participated but did so more than three months prior to consenting to Project 1 Aim 2.

Participants will be evaluated with inclusion/exclusion criteria and complete the informed consent. A medical/pain history will be taken and a physical exam will be completed by a physician. Participants will complete a number of questionnaires assessing health and medical history, past and current pain levels, and personality. Participants will have their blood drawn to confirm appropriate kidney and liver function (investigators will take \~40mL of blood). Participants will also be asked to provide a urine sample to confirm if any illicit drugs are in their system.

Participants will also be instructed to report their pain and craving ratings via an application that will be downloaded on their device. They will need to complete two ratings per day that they are involved in the study.

Visit 1, 2, and 3 (6-8 hours):

Participants will be instructed to not take their morning opioid medication. Upon arrival, participants will be asked to report their pain and craving using the Pain and Craving Index (PCI), which will be used as a baseline rating. They will complete the PCI once every hour throughout their visit. Once their PCI has increased by at least two-points from their baseline rating, the patient will undergo their first brain MRI scan (anatomical and functional scans).

Between arrival and the first MRI, participants will complete several questionnaires regarding pain, mood, thoughts, and feelings. Directly after the MRI, participants will have their blood drawn. This blood draw will be used to quantitatively analyze the participants' opioid levels. Participants will then complete the NIH Toolbox. The NIH Toolbox is a compilation of activities that evaluate different cognitive, motor and emotional functions.

Participants will then be randomized and receive "Treatment Dose #1." Treatment dose #1 will be one of the following: a single dose of the participant's opioid prescription (provided by Northwestern Memorial Hospital's investigational pharmacy), carbidopa/levodopa (c-dopa/l-dopa), or placebo (lactose). Participants will then complete the same questionnaires as they previously had, undergo a second brain MRI scan, have their blood drawn, and complete a second NIH Toolbox.

Participants will then receive "Treatment Dose #2." For those participants that received their opioid medication for treatment dose #1, they will receive placebo for their treatment dose #2. For those participants that received carbidopa/levodopa or placebo for treatment dose #1, they will receive their opioid prescription for their treatment dose #2.

After receiving treatment dose #2, participants will be done with their imaging visit.

Each participant will have three total imaging visits. The activities within each imaging visit will be identical, the only variable will be the study intervention (opioid, c-dopa/l-dopa, or placebo) that they receive. All participants will receive each of the possible study interventions; however, the sequence of when they will receive each drug will be different from participant to participant. Neither participants nor the clinical coordinator/assistant will know which intervention the participant is receiving.

Conditions

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Opioid Use Opioid Dependence Opioid-use Disorder Narcotic Use Back Pain Back Injuries Chronic Pain Chronic Low-back Pain Pain, Chronic Pain;Back Low;Chronic Pain, Back

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

There will be 2 arms of participants, those who have back pain with opioid exposure, and those who have back pain with opioid exposure and opioid misuse disorder. Each participant, regardless of the arm that they are in, will receive each of the possible study interventions. The only difference will be the order of which they receive each interventions.

Recruitment is completed. Of the collected subjects with opioid exposure none exhibited opioid misuse.
Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators
All data analysis personnel are masked regarding groupings

Study Groups

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Chronic Back Pain with Opioid Use

Subjects of this arms will be on a previously prescribed, short term acting opioid. Previous to each of the three imaging visits, subjects will be instructed to withhold from taking their regular morning opioid dose. Subjects will be randomized into a group that determines the sequence of which they will receive the study drugs. The three sequences are as follows:

1. treatment dose #1: 25mg carbidopa/ 100mg levodopa + 500mg naproxen, treatment dose #2: subjects prescribed, short acting opioid;
2. treatment dose #1: placebo, treatment dose #2: subjects prescribed, short acting opioid; or
3. treatment #1: subjects prescribed, short acting opioid, treatment dose #2: placebo.

Group Type EXPERIMENTAL

Carbidopa-Levodopa 25 Mg-100 Mg Oral Tablet

Intervention Type DRUG

Subjects will receive a single dose of carbidopa/levodopa, when applicable.This will be double-blinded, as neither participants nor study staff will know what medication the participant is receiving.

Naproxen 500 Mg

Intervention Type DRUG

Subjects will receive a single dose of naproxen 500mg alongside carbidopa/levodopa, when applicable.This will be double-blinded, as neither participants nor study staff will know what medication the participant is receiving.

Opioids

Intervention Type DRUG

Subjects will be pre-screened in regards to their opioid medication. They will receive a single dose of their opioid dose, when appropriate. This will be double-blinded, as neither participants nor study staff will know what medication the participant is receiving.

Chronic Back Pain with Opioid Misuse Disorder

Subjects of this arms will be on a previously prescribed, short term acting opioid. Previous to each of the three imaging visits, subjects will be instructed to withhold from taking their regular morning opioid dose. Subjects will be randomized into a group that determines the sequence of which they will receive the study drugs. The three sequences are as follows:

1. treatment dose #1: 25mg carbidopa/ 100mg levodopa + 500mg naproxen, treatment dose #2: subjects prescribed, short acting opioid;
2. treatment dose #1: placebo, treatment dose #2: subjects prescribed, short acting opioid; or
3. treatment #1: subjects prescribed, short acting opioid, treatment dose #2: placebo.

Group Type EXPERIMENTAL

Carbidopa-Levodopa 25 Mg-100 Mg Oral Tablet

Intervention Type DRUG

Subjects will receive a single dose of carbidopa/levodopa, when applicable.This will be double-blinded, as neither participants nor study staff will know what medication the participant is receiving.

Naproxen 500 Mg

Intervention Type DRUG

Subjects will receive a single dose of naproxen 500mg alongside carbidopa/levodopa, when applicable.This will be double-blinded, as neither participants nor study staff will know what medication the participant is receiving.

Opioids

Intervention Type DRUG

Subjects will be pre-screened in regards to their opioid medication. They will receive a single dose of their opioid dose, when appropriate. This will be double-blinded, as neither participants nor study staff will know what medication the participant is receiving.

Interventions

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Carbidopa-Levodopa 25 Mg-100 Mg Oral Tablet

Subjects will receive a single dose of carbidopa/levodopa, when applicable.This will be double-blinded, as neither participants nor study staff will know what medication the participant is receiving.

Intervention Type DRUG

Naproxen 500 Mg

Subjects will receive a single dose of naproxen 500mg alongside carbidopa/levodopa, when applicable.This will be double-blinded, as neither participants nor study staff will know what medication the participant is receiving.

Intervention Type DRUG

Opioids

Subjects will be pre-screened in regards to their opioid medication. They will receive a single dose of their opioid dose, when appropriate. This will be double-blinded, as neither participants nor study staff will know what medication the participant is receiving.

Intervention Type DRUG

Other Intervention Names

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Sinemet Aleve Anaprox Antalgin Midol Extended Relief Naprosyn Soproxen Synflex Xenobid hydrocodone/acetaminophen oxycodone/acetaminophen oxycodone oxymorphone morphine codeine tramadol

Eligibility Criteria

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Inclusion Criteria

* History of low back pain for a minimum of 6 months daily (prior to screening), meeting the Quebec Task Force Classification System symptom categories I-III;
* Male or female, age equal or greater than 18 years, with no racial/ethnic restrictions;
* Must be able to read and speak English and be willing to read and understand instructions as well as questionnaires;
* Must be in generally stable health;
* Must sign an informed consent document after a complete explanation of the study documenting that they understand the purpose of the study, procedures to be undertaken, possible benefits and potential risks, and are willing to participate;
* Must have, on average ≥ 4/10 units of pain intensity over the course of a 1-4 week period prior to the brain scanning visit;
* Must be willing to complete daily smartphone/computer eDiary ratings;
* Must be on regular opioid therapy or for at least 3 months prior to randomization which will be up to the clinical investigator's decision
* Must be on a short acting opioid therapy (anticipated duration of action \< 6 hours)

Exclusion Criteria

* Low back pain associated with any systemic signs or symptoms, e.g., fever, chills;
* Other comorbid chronic pain or neurological conditions;
* Use of therapeutic doses of antidepressant medications at unstable doses (i.e., tricyclic depressants, SSRIs, SNRIs; low doses used for sleep may be allowed);
* Significant other unstable medical disease such as diabetes, congestive heart failure, coronary or peripheral vascular disease, chronic obstructive lung disease, or malignancy;
* Uncontrolled hypertension;
* Renal insufficiency;(correlated creatinine clearance \< 40mL/min or serum creatinine ≥2)
* Daily use of high doses of opioids,, as defined as \> 50mg morphine equivalent/day;
* Any medical condition that in the investigator's judgment may prevent the individual from completing the study or put the individual at undue risk;
* In the judgment of the investigator, unable or unwilling to follow protocol and instructions;
* Evidence of poor treatment compliance, in the judgment of the investigator;
* Intra-axial implants (e.g. spinal cord stimulators or pumps);
* Pregnancy, or inability to use an effective form of contraception in women of child-bearing age;
* An established diagnosis of diabetes (type 1 or type 2)
* Lactose intolerance
* History of an allergic reaction to naproxen or any NSAID;
* History of any untoward reaction to carbidopa/levodopa
* Use of a patch or long acting opioid therapy (e.g. anticipated duration of action \> 6 hours)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Shirley Ryan AbilityLab

OTHER

Sponsor Role collaborator

National Institutes of Health (NIH)

NIH

Sponsor Role collaborator

Northwestern University

OTHER

Sponsor Role lead

Responsible Party

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Apkar Apkarian

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Apkar V Apkarian, PhD

Role: PRINCIPAL_INVESTIGATOR

Northwestern University Feinberg School of Medicine

Locations

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Northwestern University Feinberg School of Medicine

Chicago, Illinois, United States

Site Status

Countries

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United States

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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STU00209670

Identifier Type: -

Identifier Source: org_study_id