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

NCT05463367 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: STU00209670
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

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

Keywords

norco; opioid; pain medication; tramadol; oxycodone; pain; chronic pain; chronic back pain; back pain; narcotics

Outcome Measures

Primary Outcomes (2)

• Differences across drugs in Withdrawal relief assessed by Pain and Craving Index (PCI).

  Pain and Drug craving Index (PCI) will be used to evaluate self-reported medication cravings. Participants will complete the scale, before and after receiving the visit drug treatment. Changes in PCI scores (after minus before) will be compared between drugs (opioids vs. placebo vs. Carbidopa/Levodopa +naproxen).

  3 weeks

• Differences across drugs in pain changes as assessed by Numeric Rating Scale (0-10).

  NRS scale will be used to evaluate self-reported pain. Participants will rate their pain before and after receiving the visit drug treatment. Changes in pain scores (after minus before) will be compared between drugs (opioids vs. placebo vs. Carbidopa/Levodopa +naproxen).

  3 weeks

Secondary Outcomes (3)

• Differences in pain changes (NRS) across High and Low Misuse groups measured by the Current Opioid Misuse Measure (COMM).

  3 weeks

• Differences in withdrawal changes (PCI) across High and Low Misuse groups measured by the Current Opioid Misuse Measure (COMM).

  3 weeks

• Whole-cortex multi-receptor related activity

  3 weeks

Study Arms (2)

Chronic Back Pain with Opioid Use

EXPERIMENTAL

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.

Drug: Carbidopa-Levodopa 25 Mg-100 Mg Oral Tablet; Drug: Naproxen 500 Mg; Drug: Opioids

Chronic Back Pain with Opioid Misuse Disorder

EXPERIMENTAL

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.

Drug: Carbidopa-Levodopa 25 Mg-100 Mg Oral Tablet; Drug: Naproxen 500 Mg; Drug: Opioids

Interventions

Carbidopa-Levodopa 25 Mg-100 Mg Oral Tablet 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.

Also known as: Sinemet

Chronic Back Pain with Opioid Misuse Disorder; Chronic Back Pain with Opioid Use

Naproxen 500 Mg 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.

Also known as: Aleve, Anaprox, Antalgin, Midol Extended Relief, Naprosyn, Soproxen, Synflex, Xenobid

Chronic Back Pain with Opioid Misuse Disorder; Chronic Back Pain with Opioid Use

Opioids 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.

Also known as: hydrocodone/acetaminophen, oxycodone/acetaminophen, oxycodone, oxymorphone, morphine, codeine, tramadol

Chronic Back Pain with Opioid Misuse Disorder; Chronic Back Pain with Opioid Use

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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;

Sponsors & Collaborators

• Northwestern University: lead
• Shirley Ryan AbilityLab: collaborator
• National Institutes of Health (NIH): collaborator

Study Sites (1)

Northwestern University Feinberg School of Medicine

Chicago, Illinois, 60611, United States

Location

MeSH Terms

Conditions

Opioid-Related Disorders; Back Pain; Back Injuries; Chronic Pain; Pain

Interventions

carbidopa, levodopa drug combination; Naproxen; Analgesics, Opioid; oxycodone-acetaminophen; Oxycodone; Oxymorphone; Morphine; Codeine; Tramadol

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Naphthaleneacetic Acids; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Narcotics; Central Nervous System Depressants; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Central Nervous System Agents; Therapeutic Uses; Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Cyclohexanols; Hexanols; Fatty Alcohols; Alcohols; Dimethylamines; Methylamines; Amines; Lipids

Study Officials

• Apkar V Apkarian, PhD

  Northwestern University Feinberg School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: All data analysis personnel are masked regarding groupings
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: 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.

Study Record Dates

• First Submitted: February 27, 2020
• First Posted: July 19, 2022
• Study Start: January 1, 2021
• Primary Completion: June 1, 2025
• Study Completion: June 1, 2025
• Last Updated: November 27, 2024

Record last verified: 2024-11

Locations

US (1)