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

Pain, Chronic Clinical Trial

— NEPAL  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02488863
• Other study ID #: IRB201401056-N
• Secondary ID: K01AG048259P30AG
• Status: Completed
• Start date: July 2015
• Est. completion date: February 4, 2024

Study information

• Verified date: April 2023
• Source: University of Florida
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 195
• Est. completion date: February 4, 2024
• Est. primary completion date: February 4, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Chronic Pain
• Musculoskeletal Pain
• Pain, Chronic

Intervention

Other:
• MRI Neuroimaging
MRI scans utilized to measure the structural and functional integrity of the brain.
• 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.
• 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).
• 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.

Locations

Country	Name	City	State
United States	Clinical Translational Research Building	Gainesville	Florida
United States	McKnight Brain Institute of the University of Florida	Gainesville	Florida
United States	UF & Shands Orthopaedics and Sports Medicine Institute	Gainesville	Florida
United States	UF Health Science Center	Gainesville	Florida

Sponsors (3)

Lead Sponsor	Collaborator
University of Florida	National Institute on Aging (NIA), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	MRI Neuroimaging	Brain connectivity, white matter connectivity indices.	At the imaging visit (2 hrs)
Primary	Quantitative Sensory Testing (QST), Vibratory Detection Thresholds	The "TSA Thermal Sensory and Vibratory Sensory Analyzer (Model TSA II, VSA 3000) (Medoc. LTD)" will be used in this study to quantify nerve fiber dysfunction with measurements of vibratory thresholds. Vibratory threshold is tested with a vibratory pin, which presses the measured area with a consistent pressure of 50g. The vibratory sense analysis will be performed with upward-moving stimuli, which increases in intensity until a sensation is perceived. Several vibrations will be given sequentially and the mean end variance will be determined to verify the consistency of the test.	At the QST visit (2 hrs)
Primary	Quantitative Sensory Testing (QST), Tactile Detection Thresholds	Thresholds for light touch will be assessed with von Frey monofilaments, using two ascending and two descending stimulus series, according to the method of limits. Detection threshold at each test site will be determined by the obtaining the geometric mean across these four test series.	At the QST visit (2 hrs)
Primary	Quantitative Sensory Testing (QST), Thermal Detection Thresholds, Pain Thresholds, and Temporal Summation	The "TSA Thermal Sensory and Vibratory Sensory Analyzer (Model TSA II, VSA 3000) (Medoc. LTD)" will also be used in this study to quantify nerve fiber dysfunction with measurements of thermal sensory thresholds (warm, cold, heat-induced pain, and cold-induced pain). Several trials will be performed for the sensory modality and a mean threshold will be calculated. For threshold determination, the investigators will use a "reaction time-inclusive" method, the method of limits, consisting of continuously changing intensities of stimuli halted automatically by the subject at the moment that the requested sensation is perceived. The following thresholds will be evaluated using the TSA II: (1) cool sensation; (2) warm sensation; (3) cold pain; and (4) heat pain. Subjects will also be asked to qualify the sensation after it has been quantified. Temporal summation of heat pain will be assessed by administering brief repetitive suprathreshold heat stimuli to test sites.	At the QST visit (2 hrs)
Primary	Quantitative Sensory Testing (QST), Allodynia and Temporal Summation	Dynamic mechanical allodynia will be investigated using a soft brush and lightly brushing the skin of the hands and feet as well as any reported painful areas. If pain is evoked in the test area, the participant will be asked to rate the intensity of the pain. If an allodynic area is detected, temporal summation will be evoked by repetitively tapping the skin of the allodynic area with von Frey hairs (100g) at 1 Hz for 10 seconds. If temporal summation is evoked in the allodynic test area the participant will be asked to rate the intensity of the pain.	At the QST visit (2 hrs)
Primary	Quantitative Sensory Testing (QST), Punctate Pain Testing and Temporal Summation	We will apply punctate mechanical stimuli to the test sites with a series of weighted probes. Probes of different weights will be applied to participants' skin to determine the level that produces slight discomfort or pain. Two measures are obtained: 1) Pain threshold is determined by applying probes of different weights in ascending and descending sequences and participants are asked to tell the examiner which probes produce pain; 2) A weighted probe is applied either once or several times in a row and participants are asked to rate the pain they experience from the probe. In addition, a standardized plastic MediPin ® commonly used in neurological examinations will be applied to testing areas and participants will be asked to rate the intensity of any pain that is experienced.	At the QST visit (2 hrs)
Primary	Quantitative Sensory Testing (QST), Pressure Pain Thresholds	Pressure is delivered by a hand-held algometer (FDX, Wagner Instruments and/or Algomed, Medoc LTD), which is a spring-controlled device that delivers calibrated pressure via a flat 10mm diameter rubber tip. Pressure is delivered at an approximate rate of 1 kg/sec. Participants respond when they first feel pain, at which time the pressure is removed.	At the QST visit (2 hrs)
Primary	Upper Limb Isometric Strength	This is a handgrip strength test using a dynamometer. The subject will be instructed to squeeze the dynamometer with maximum isometric effort for about 5 seconds. No other body movement will be allowed.	At the Physical and Cognitive Function visit (2 hrs)
Primary	Short Physical Performance Battery (SPPB)	The SPPB is based on a timed short distance walk, repeated chair stands and a balance test, which will be administered by a well-trained study team member.	At the Physical and Cognitive Function visit (2 hrs)
Primary	Mobility Assessments	Participants will be asked to walk over a mat without any obstacles, as well as stepping over an obstacle, and while performing a cognitive task. Some tests will be performed while walking over a GAITRite ® instrumented walking mat, which measures spatiotemporal gait parameters.	At the Physical and Cognitive Function visit (2 hrs)
Primary	Galvanic Skin Response	Changes in participants' skin conductance will be measured (Biograph® ProComp5TM Infinity) during mobility assessments. Conductive electrodes will be attached to participants' fingers to measure any emotional arousal elicited by obstacles and/or cognitive tasks.	At the Physical and Cognitive Function visit (2 hrs)
Primary	Pepper Assessment Tool for Disability (PAT-D)	The PAT-D is a validated questionnaire which consists of 5 subscales: mobility, transferring, upper extremity, instrumental and basic activities of daily living.	At the Physical and Cognitive Function visit (2 hrs)
Primary	Knee Extension Isokinetic Strength	An isokinetic dynamometer modified with increased sensitivity force transducers will be used to record Total work (Joules) and maximal force production (Biodex System 3, Shirley, NY). Participants will move through a full range of motion (if no contraindications are present), performing contractions at 60, 90 and 120 degrees/second to document potential effects on the velocity of movement.	At the Physical and Cognitive Function visit (2 hrs)
Primary	NIH Cognition Toolbox	The NIH Cognition toolbox assesses cognitive functions.	At the Physical and Cognitive Function visit (2 hrs)
Secondary	The Modified Mini-Mental State Examination (3MS)	The 3MS screens for cognitive impairment.	At the baseline/screening visit (2 hrs)
Secondary	The Montreal Cognitive Assessment (MoCA)	The MoCA assesses multiple domains of cognitive functions.	At the baseline/screening visit (2 hrs)
Secondary	Center for Epidemiologic Studies Depression Scale (CES-D)	The CES-D screens for depression.	At the baseline/screening visit and at 12 month follow-up
Secondary	Geriatric Depression Scale (GDS)	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
Secondary	Edinburg Handedness Inventory	The Edinburg Handedness Inventory assesses which hand is dominant.	At the baseline/screening visit (2 hrs)
Secondary	The Ten-Item Personality Inventory (TIPI)	The TIPI is a 10-item measure of the Big Five (or Five-Factor Model) dimensions.	At the baseline/screening visit (2 hrs)
Secondary	The Pittsburgh Sleep Quality Index (PSQI)	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
Secondary	The trait version of the State-Trait Anxiety Inventory (STAI)	The STAI is an introspective psychological inventory consisting of 40 self-report items pertaining to anxiety affect.	At the baseline/screening visit (2 hrs)
Secondary	The trait version of the Positive and Negative Affect Schedule (PANAS)	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)
Secondary	Knee X-ray	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)
Secondary	The state version of the State-Trait Anxiety Inventory (STAI)	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
Secondary	The state version of the Positive and Negative Affect Schedule (PANAS)	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
Secondary	The Graded Chronic Pain Scale (GCPS)	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
Secondary	The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)	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
Secondary	Pain DETECT	The Pain DETECT questionnaire screens for neuropathic components of pain.	At the baseline/screening visit and at 12 month follow-up
Secondary	Short Form-McGill Pain Questionnaire (SF-MPQ)	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
Secondary	Coping Strategies Questionnaire- Revised (CSQ-R)	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
Secondary	Hopkins Verbal Learning Test (HVLT)	The HVLT measures verbal memory.	At the baseline/screening visit (2 hrs)
Secondary	Trail Making A & B	The Trail Making Test measures set shifting and psychomotor speed.	At the baseline/screening visit (2 hrs)
Secondary	Boston Naming Test	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)
Secondary	Controlled Oral Word Association (COWA) Test	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)
Secondary	The Stroop Interference test	The Stroop Interference test assesses cognitive functions.	At the baseline/screening visit (2 hrs)
Secondary	The Ruff Figural Fluency test	The Ruff Figural Fluency test is a nonverbal measure of initiation, planning, and divergent reasoning.	At the baseline/screening visit (2 hrs)
Secondary	Raven's Standard Progressive Matrices (SPM)	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)