NEPAL (Neuromodulatory Examination of Pain and Mobility Across the Lifespan) (NEPAL)

March 11, 2025 updated by: University of Florida

Neuroimaging Age-related Versus Pain-related Changes in Pain Modulation

Musculoskeletal pain represents the leading cause of disability worldwide. It has been traditionally attributed to peripheral mechanisms, but peripheral damage, inflammation, and psychological factors have failed to significantly account for the presence, absence, or severity of chronic musculoskeletal pain (CMP). Recent studies show that individuals with CMP exhibit dysfunctional pain modulation supporting a significant central nervous system (CNS) contribution. However, the CNS mechanisms underlying these changes in pain modulation are not currently known, nor is their relation to clinical pain progression. The proposed pilot examines brain circuits recently described in predicting the transition from acute to chronic pain, in predicting clinical and experimental pain changes as well as physical performance and mobility changes in older persons with musculoskeletal pain over a one year period. The findings will provide novel and important information regarding the mechanisms underlying aberrant pain processing and its functional consequences in older adults with musculoskeletal pain. The information learned can be subsequently used to target treatment and prevention strategies in future studies of older adults. The central hypothesis is that increased functional and structural connectivity of cortico-striatal regions will be significantly associated with baseline clinical and experimental pain and decreased physical function in persons with CMP and will account for more rapid clinical pain and disability progression over time.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Chronic musculoskeletal pain (CMP) is the most common, non-malignant disabling condition that affects at least one in four older people. The most common painful musculoskeletal conditions among older adults are osteoarthritis, low back pain, fibromyalgia, chronic shoulder pain, knee pain, myofascial pain syndrome and previous fracture sites. Recent studies demonstrate generalized alterations of pain processing among older individuals with CMP. An improved understanding of the mechanisms underlying CMP-related changes in pain modulation will provide a basis for the development of targeted preventive and rehabilitative strategies. In light of evidence emphasizing plasticity of white matter connections, and the potential pain relieving effects of non-invasive brain stimulation interventions, it seems reasonable to identify these connections as potential targets for future treatment approaches. Given the expected growth of the older population, such strategies could have a monumental impact in reducing healthcare expenditures and improving the quality of life of older adults.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
105

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • Florida
      • Gainesville, Florida, United States, 32607
        • UF & Shands Orthopaedics and Sports Medicine Institute
      • Gainesville, Florida, United States, 32608
        • UF Health Science Center
      • Gainesville, Florida, United States, 32611
        • McKnight Brain Institute of the University of Florida
      • Gainesville, Florida, United States, 32611
        • Clinical Translational Research Building

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

Older adults (60+ years old) who experience musculoskeletal pain as well as those who do not experience musculoskeletal pain; healthy young adults (18-25 years old).

Description

Inclusion Criteria:

  • older adults over 60 years of age with and without musculoskeletal pain
  • healthy young adults between the ages of 18-25

Exclusion Criteria:

  • pregnant women
  • history of alcohol/drug abuse in the past
  • known intra-cerebral pathology or epilepsy
  • significant cognitive impairment as evidenced by the 3MS
  • hospitalizations for mental health reasons in the past year
  • not meeting MRI screening requirements (implants, prosthesis, artificial limb/joint, shunt, metal rods, hearing aid, claustrophobia or anxiety)
  • chronic/current use of narcotic medications
  • serious systemic (uncontrolled diabetes; self reported A1C>7), neurological , or cardiovascular disease (uncontrolled hypertension >155/90)
  • liver or kidney disease
  • inability to consent for study participation

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Control
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Older Adults with Musculoskeletal Pain
Older adults (60+ years old) experiencing musculoskeletal pain will undergo: MRI Neuroimaging, Quantitative Sensory Testing, Physical and Cognitive Function Testing, and questionnaire batteries.
Other: MRI Neuroimaging
MRI scans utilized to measure the structural and functional integrity of the brain.
Other Names:
  • Functional Magnetic Resonance Imaging (fMRI)
Other: Quantitative Sensory Testing
Vibratory Detection Thresholds; Tactile Detection Thresholds; Thermal Detection Thresholds, Pain Thresholds, and Temporal Summation; Allodynia and Temporal Summation; Punctate Pain Testing and Temporal Summation; and Pressure Pain Thresholds.
Other Names:
  • QST
Other: Questionnaires
The Modified Mini-Mental State Examination (3MS), the Montreal Cognitive Assessment (MoCA), the Center for Epidemiologic Studies Depression Scale (CES-D), the Geriatric Depression Scale (GDS), the Edinburg Handedness Inventory, the Ten-Item Personality Inventory (TIPI), the Pittsburgh Sleep Quality Index (PSQI), the state and trait versions of the State-Trait Anxiety Inventory (STAI), the state and trait versions of the Positive and Negative Affect Schedule (PANAS), pain questionnaires (the Graded Chronic Pain Scale (GCPS), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Pain-Detect, the short-form McGill Pain Questionnaire (SF-MPQ-2), and the Coping Strategies Questionnaire-Revised (CSQ-R)), a standardized paper and pencil cognitive battery (Hopkins Verbal Learning Test (HVLT), Trail Making A&B, Boston Naming Test, Controlled Oral Word Association Test (COWAT), Stroop Interference Test, Ruff Figural Fluency Test, and Raven's Progressive Matrices Test).
Other: Physical and Cognitive Function Testing
Upper Limb Isometric Strength, Short Physical Performance Battery (SPPB), GAITRite Instrumented Walking, Galvanic Skin Response, Knee Extension Isokinetic Strength, the Pepper Assessment Tool for Disability (PAT-D), and an electronic NIH Toolbox Cognitive Battery.
Older Adults without Musculoskeletal Pain
Older adults (60+ years old) not experiencing musculoskeletal pain will undergo: MRI Neuroimaging, Quantitative Sensory Testing, Physical and Cognitive Function Testing, and questionnaire batteries.
Other: MRI Neuroimaging
MRI scans utilized to measure the structural and functional integrity of the brain.
Other Names:
  • Functional Magnetic Resonance Imaging (fMRI)
Other: Quantitative Sensory Testing
Vibratory Detection Thresholds; Tactile Detection Thresholds; Thermal Detection Thresholds, Pain Thresholds, and Temporal Summation; Allodynia and Temporal Summation; Punctate Pain Testing and Temporal Summation; and Pressure Pain Thresholds.
Other Names:
  • QST
Other: Questionnaires
The Modified Mini-Mental State Examination (3MS), the Montreal Cognitive Assessment (MoCA), the Center for Epidemiologic Studies Depression Scale (CES-D), the Geriatric Depression Scale (GDS), the Edinburg Handedness Inventory, the Ten-Item Personality Inventory (TIPI), the Pittsburgh Sleep Quality Index (PSQI), the state and trait versions of the State-Trait Anxiety Inventory (STAI), the state and trait versions of the Positive and Negative Affect Schedule (PANAS), pain questionnaires (the Graded Chronic Pain Scale (GCPS), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Pain-Detect, the short-form McGill Pain Questionnaire (SF-MPQ-2), and the Coping Strategies Questionnaire-Revised (CSQ-R)), a standardized paper and pencil cognitive battery (Hopkins Verbal Learning Test (HVLT), Trail Making A&B, Boston Naming Test, Controlled Oral Word Association Test (COWAT), Stroop Interference Test, Ruff Figural Fluency Test, and Raven's Progressive Matrices Test).
Other: Physical and Cognitive Function Testing
Upper Limb Isometric Strength, Short Physical Performance Battery (SPPB), GAITRite Instrumented Walking, Galvanic Skin Response, Knee Extension Isokinetic Strength, the Pepper Assessment Tool for Disability (PAT-D), and an electronic NIH Toolbox Cognitive Battery.
Young Controls
Healthy young adults (18-25 years old) not experiencing musculoskeletal pain will undergo: MRI Neuroimaging, Quantitative Sensory Testing, Physical and Cognitive Function Testing, and questionnaire batteries.
Other: MRI Neuroimaging
MRI scans utilized to measure the structural and functional integrity of the brain.
Other Names:
  • Functional Magnetic Resonance Imaging (fMRI)
Other: Quantitative Sensory Testing
Vibratory Detection Thresholds; Tactile Detection Thresholds; Thermal Detection Thresholds, Pain Thresholds, and Temporal Summation; Allodynia and Temporal Summation; Punctate Pain Testing and Temporal Summation; and Pressure Pain Thresholds.
Other Names:
  • QST
Other: Questionnaires
The Modified Mini-Mental State Examination (3MS), the Montreal Cognitive Assessment (MoCA), the Center for Epidemiologic Studies Depression Scale (CES-D), the Geriatric Depression Scale (GDS), the Edinburg Handedness Inventory, the Ten-Item Personality Inventory (TIPI), the Pittsburgh Sleep Quality Index (PSQI), the state and trait versions of the State-Trait Anxiety Inventory (STAI), the state and trait versions of the Positive and Negative Affect Schedule (PANAS), pain questionnaires (the Graded Chronic Pain Scale (GCPS), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Pain-Detect, the short-form McGill Pain Questionnaire (SF-MPQ-2), and the Coping Strategies Questionnaire-Revised (CSQ-R)), a standardized paper and pencil cognitive battery (Hopkins Verbal Learning Test (HVLT), Trail Making A&B, Boston Naming Test, Controlled Oral Word Association Test (COWAT), Stroop Interference Test, Ruff Figural Fluency Test, and Raven's Progressive Matrices Test).
Other: Physical and Cognitive Function Testing
Upper Limb Isometric Strength, Short Physical Performance Battery (SPPB), GAITRite Instrumented Walking, Galvanic Skin Response, Knee Extension Isokinetic Strength, the Pepper Assessment Tool for Disability (PAT-D), and an electronic NIH Toolbox Cognitive Battery.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Short Physical Performance Battery (SPPB)
Time Frame: At baseline-physical function visit
The Short Physical Performance Battery (SPPB) Total Score is a measure of physical function. It is calculated by summing three measures of lower-extremity function: standing balance (side-by-side, semi-tandem, and tandem stance), 4-meter walking speed, and ability to rise from a chair. Each task is rated on a 0-4 scale, with increasing scores indicating better physical performance. The SPPB Total scores range from 0-12.
At baseline-physical function visit

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
The Modified Mini-Mental State Examination (3MS)
Time Frame: At the baseline/screening visit (2 hrs)
The 3MS screens for cognitive impairment.
At the baseline/screening visit (2 hrs)
The Montreal Cognitive Assessment (MoCA)
Time Frame: At the baseline/screening visit (2 hrs)
The MoCA assesses multiple domains of cognitive functions.
At the baseline/screening visit (2 hrs)
Center for Epidemiologic Studies Depression Scale (CES-D)
Time Frame: At the baseline/screening visit and at 12 month follow-up
The CES-D screens for depression.
At the baseline/screening visit and at 12 month follow-up
Geriatric Depression Scale (GDS)
Time Frame: At the baseline/screening visit and at 12 month follow-up
The GDS is a 30-item self-report assessment used to identify depression in the elderly.
At the baseline/screening visit and at 12 month follow-up
Edinburg Handedness Inventory
Time Frame: At the baseline/screening visit (2 hrs)
The Edinburg Handedness Inventory assesses which hand is dominant.
At the baseline/screening visit (2 hrs)
The Ten-Item Personality Inventory (TIPI)
Time Frame: At the baseline/screening visit (2 hrs)
The TIPI is a 10-item measure of the Big Five (or Five-Factor Model) dimensions.
At the baseline/screening visit (2 hrs)
The Pittsburgh Sleep Quality Index (PSQI)
Time Frame: At the baseline/screening visit and at 12 month follow-up
The PSQI is an instrument used to measure the quality and patterns of sleep in adults.
At the baseline/screening visit and at 12 month follow-up
The trait version of the State-Trait Anxiety Inventory (STAI)
Time Frame: At the baseline/screening visit (2 hrs)
The STAI is an introspective psychological inventory consisting of 40 self-report items pertaining to anxiety affect.
At the baseline/screening visit (2 hrs)
The trait version of the Positive and Negative Affect Schedule (PANAS)
Time Frame: At the baseline/screening visit (2 hrs)
The PANAS is a self-report questionnaire that consists of two 10-item scales to measure both positive and negative affect.
At the baseline/screening visit (2 hrs)
Knee X-ray
Time Frame: At the baseline/screening visit (2 hrs)
For older adult cohorts (ages 60+), an x-ray of the dominant knee will be taken to measure presence/severity of osteoarthritis.
At the baseline/screening visit (2 hrs)
The state version of the State-Trait Anxiety Inventory (STAI)
Time Frame: At the baseline/screening visit, at each experimental visit, and at 12 month follow-up
The STAI is an introspective psychological inventory consisting of 40 self-report items pertaining to anxiety affect.
At the baseline/screening visit, at each experimental visit, and at 12 month follow-up
The state version of the Positive and Negative Affect Schedule (PANAS)
Time Frame: At the baseline/screening visit, at each experimental visit, and at 12 month follow-up
The PANAS is a self-report questionnaire that consists of two 10-item scales to measure both positive and negative affect.
At the baseline/screening visit, at each experimental visit, and at 12 month follow-up
The Graded Chronic Pain Scale (GCPS)
Time Frame: At the baseline/screening visit, at each experimental visit, and at 12 month follow-up
The GCPS is a seven-item instrument designed to evaluate overall severity of chronic pain based on two dimensions, pain intensity and pain-related disability.
At the baseline/screening visit, at each experimental visit, and at 12 month follow-up
The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)
Time Frame: At the baseline/screening visit and at 12 month follow-up
The WOMAC questionnaire evaluates the condition of osteoarthritis, including pain, stiffness, and physical functioning of the joints.
At the baseline/screening visit and at 12 month follow-up
Pain DETECT
Time Frame: At the baseline/screening visit and at 12 month follow-up
The Pain DETECT questionnaire screens for neuropathic components of pain.
At the baseline/screening visit and at 12 month follow-up
Short Form-McGill Pain Questionnaire (SF-MPQ)
Time Frame: At the baseline/screening visit and at 12 month follow-up
The SF-MPQ consists of 15 sensory and affective descriptors of pain that are rated on an intensity scale.
At the baseline/screening visit and at 12 month follow-up
Coping Strategies Questionnaire- Revised (CSQ-R)
Time Frame: At the baseline/screening visit and at 12 month follow-up
The Coping Strategies Questionnaire measures pain coping strategies on a 7-point Likert Scale.
At the baseline/screening visit and at 12 month follow-up
Hopkins Verbal Learning Test (HVLT)
Time Frame: At the baseline/screening visit (2 hrs)
The HVLT measures verbal memory.
At the baseline/screening visit (2 hrs)
Trail Making A & B
Time Frame: At the baseline/screening visit (2 hrs)
The Trail Making Test measures set shifting and psychomotor speed.
At the baseline/screening visit (2 hrs)
Boston Naming Test
Time Frame: At the baseline/screening visit (2 hrs)
The Boston Naming test includes 60 line drawings ranging from simple, high frequency vocabulary (i.e. tree) to rare words (abascus).
At the baseline/screening visit (2 hrs)
Controlled Oral Word Association (COWA) Test
Time Frame: At the baseline/screening visit (2 hrs)
The COWA Test is a verbal fluency test that measures spontaneous production of words belonging to the same category or beginning with some designated letter.
At the baseline/screening visit (2 hrs)
The Stroop Interference test
Time Frame: At the baseline/screening visit (2 hrs)
The Stroop Interference test assesses cognitive functions.
At the baseline/screening visit (2 hrs)
The Ruff Figural Fluency test
Time Frame: At the baseline/screening visit (2 hrs)
The Ruff Figural Fluency test is a nonverbal measure of initiation, planning, and divergent reasoning.
At the baseline/screening visit (2 hrs)
Raven's Standard Progressive Matrices (SPM)
Time Frame: At the baseline/screening visit (2 hrs)
The SPMs were developed to assess, as simply and unambiguously as possible, the two components of "g"--or "general" factor in mental ability--identified by Spearman as eductive ability and reproductive ability.
At the baseline/screening visit (2 hrs)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Florida

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Institutes of Health (NIH)
National Institute on Aging (NIA)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Yenisel Cruz-Almeida, MSPH, PhD, University of Florida

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 1, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 4, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 4, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 23, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 1, 2015

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 2, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 25, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 11, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • IRB201401056-N
  • K01AG048259 (U.S. NIH Grant/Contract)
  • P30AG059297 (U.S. NIH Grant/Contract)
  • Pepper Grant (Other Grant/Funding Number: National Institute of Health)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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