The Role of Brain Dopamine in Chronic Pain

NCT05285683 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: STUDY00006948
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Chronic pain is associated with plasticity in the brain limbic system composed mainly of the amygdala, hippocampus, ventral striatum, and cingulate cortex (ACC) /medial prefrontal cortex (mPFC). These brain areas, especially the ventral striatum, receive dopaminergic input from the ventral-tegmental area (VTA). Although there is a significant literature now showing that limbic brain tracks chronic pain intensity and predicts the risk of transition from sub-acute to chronic pain, the role of dopaminergic input to the limbic brain and the change thereof which occurs in chronic pain, is still not clear. Given the role of dopamine in motivational control and the loss of motivation associated with chronic pain understanding how dopaminergic transmission is altered in the limbic brain of chronic pain patients is critical to the understanding of the pathophysiology of chronic pain. Therefore, the overall aim of this project is to use brain imaging to study how dopaminergic transmission through the oral administration of pro-dopaminergic medications carbidopa/levodopa (CD/LD) and methylphenidate will modulate the brain signature of chronic pain. Chronic pain subjects will be scanned at baseline (no drug administration) and three times after treatment with the two drugs or placebo. The protocol will follow a randomized double-blind approach.

Conditions

Chronic Pain

Keywords

dopamine; loss of motivation; chronic back pain

Outcome Measures

Primary Outcomes (8)

• mean change in amygdala volume

  Amygdala volume will be measured using T1w MPRAGE structural images. The mean change in amygdala volume will be the volume of amygdala before administering the drug or placebo minus the volume of amygdala after administering the drug or placebo.

  baseline to 3 hours

• mean change in hippocampus volume

  Hippocampus volume will be measured using T1w MPRAGE structural images. The mean change in hippocampus volume will be the volume of hippocampus before administering the drug or placebo minus the volume of hippocampus after administering the drug or placebo.

  baseline to 3 hours

• mean change in thalamus volume

  Thalamus volume will be measured using T1w MPRAGE structural images. The mean change in thalamus volume will be the volume of thalamus before administering the drug or placebo minus the volume of thalamus after administering the drug or placebo.

  baseline to 3 hours

• mean change in Nucleus accumbens volume

  Nucleus accumbens volume will be measured using T1w MPRAGE structural images. The mean change in Nucleus accumbens volume will be the volume of Nucleus accumbens before administering the drug or placebo minus the volume of Nucleus accumbens after administering the drug or placebo.

  baseline to 3 hours

• mean change in amygdala activity

  Amygdala activity will be determined using Blood Oxygen Level Dependent (BOLD) fMRI sequences. The mean change in amygdala activity will be the activity of amygdala before administering the drug or placebo minus the activity of amygdala after administering the drug or placebo.

  baseline to 3 hours

• mean change in hippocampus activity

  Hippocampus activity will be determined using Blood Oxygen Level Dependent (BOLD) fMRI sequences. The mean change in hippocampus activity will be the activity of hippocampus before administering the drug or placebo minus the activity of hippocampus after administering the drug or placebo.

  baseline to 3 hours

• mean change in thalamus activity

  Thalamus activity will be determined using Blood Oxygen Level Dependent (BOLD) fMRI sequences. The mean change in thalamus activity will be the activity of thalamus before administering the drug or placebo minus the activity of thalamus after administering the drug or placebo.

  baseline to 3 hours

• mean change in Nucleus Accumbens activity

  Nucleus Accumbens activity will be determined using Blood Oxygen Level Dependent (BOLD) fMRI sequences. The mean change in Nucleus Accumbens activity will be the activity of Nucleus Accumbens before administering the drug or placebo minus the activity of Nucleus Accumbens after administering the drug or placebo.

  baseline to 3 hours

Secondary Outcomes (1)

• Effort Expenditure for Reward Task (EEfRT)

  baseline to 3 hours

Study Arms (3)

Methylphenidate

ACTIVE COMPARATOR

0.5mg/kg

Drug: Methylphenidate

Carbidopa/levodopa,

ACTIVE COMPARATOR

25mg/100mg

Drug: carbidopa-levodopa

Placebo

PLACEBO COMPARATOR

Oral Pill

Drug: Placebo

Interventions

Methylphenidate DRUG

0.5 mg/kg

Methylphenidate

carbidopa-levodopa DRUG

25 mg/100 mg

Carbidopa/levodopa,

Placebo DRUG

oral pill

Placebo

Eligibility Criteria

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

You may qualify if:

• years old or older
• Equal numbers of men and women, as well as racial and ethnic makeup representative of surrounding area
• Able to speak, read, and understand English
• In generally stable health
• Sign informed consent document
• Patients must report chronic pain for more than 1 year.
• The reported pain should be rated at ≥ 40/100

You may not qualify if:

• Significant other medical disease, such as unstable diabetes mellitus, congestive heart failure, coronary or peripheral vascular disease, chronic obstructive lung disease, or malignancy
• History of traumatic brain injury (TBI)
• Current misuse/dependence on substance(s), including alcohol, at the time of study enrollment
• Major psychiatric disorder during the past 6 months
• Significantly abnormal laboratory values, which include, but are not limited to, the following:
• White blood cell (WBC) \< 1.5 or \>15.0 x 10\^3/μL
• Hemoglobin (Hgb) \< 8 gm/dL
• Hematocrit (Hct) \< 24% or \> 50%
• Platelets (Plts) \<50 or \> 1000 x10\^3
• Creatine \> 2 mg/dL
• Glucose \> 125 mg/dL
• Aspartate aminotransferase (AST) \> 250 U/L
• Alanine Transaminase (ALT) \> 250 U/L
• Bilirubin \> 3 mg/dL
• Intra-axial implants (e.g. - spinal cord stimulators or pumps)

Sponsors & Collaborators

• University of Rochester: lead

Study Sites (1)

University of Rochester Medical Center

Rochester, New York, 14642, United States

RECRUITING

MeSH Terms

Conditions

Chronic Pain

Interventions

Methylphenidate; carbidopa, levodopa drug combination

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Central Study Contacts

Pain Lab

CONTACT

585-275-4424; painlab@urmc.rochester.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: February 21, 2022
• First Posted: March 17, 2022
• Study Start: January 31, 2024
• Primary Completion: December 22, 2025
• Study Completion: January 22, 2026
• Last Updated: January 15, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)