Individual Differences in Gait and Osteoarthritis Pain (INDIGO)

The goal of this observational study is to look at inter-individual differences in knee osteoarthritis (OA) walking pain and performance. The main questions this study aims to answer are:

Why do some people with knee osteoarthritis have more severe disabling pain than others, even though the degenerative changes in their knees are similar?

What are the factors that contribute to walking pain in people with knee osteoarthritis?

Participants will complete surveys, perform physical function tasks, get a knee X-ray and MRI, undergo non-invasive brain imaging, and undergo sensory testing.

Study Overview

• Status: Recruiting
• Conditions: Chronic Pain; Chronic Knee Pain; Knee Osteoarthritis (OA)

Detailed Description

This observational study will identify biopsychosocial factors that contribute to inter-individual differences in walking pain and pain limiting walking with the hypothesis that neural processes play a key role. This study's objective is to elucidate "whole person" biopsychosocial mechanisms of movement-evoked pain and pain limitations on function in knee OA, helping to determine why some patients have severe disabling pain while others do not despite similar degenerative changes of the knee joint. Three hundred participants with knee OA will undergo a comprehensive data collection over two study visits, including surveys, exercise tasks, non-invasive brain and joint imaging, and biomechanics assessments during mobility. Using advanced analysis, this dataset will be used to identify factors contributing to walking-evoked pain and functional limitations in knee osteoarthritis.These results will identify new therapeutic targets to maintain or improve physical activity in patients with knee osteoarthritis, leading to better outcomes of physical therapy and improved overall health and well-being.

• Study Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

• Study Contact: Name: Benedict Alter, MD, PhD; Phone Number: 412-665-8052; Email: bea51@pitt.edu
• Study Contact Backup: Name: Emma Racunas, BS; Email: ecr79@pitt.edu

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15206
      • Recruiting
      • UPMC Pain Medicine at Centre Commons

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The sample includes participants with knee osteoarthritis of at least moderate pain severity and radiographic evidence of significant knee joint degeneration. Participants will be recruited from research registries (Pitt CTSI Pitt+Me) and clinics with a high volume of knee osteoarthritis patients, including orthopedic and pain management clinics. Eligibility criteria are designed to study knee osteoarthritis pain around the time of walking. Therefore, some comorbidities and pain conditions are allowed if knee osteoarthritis is the primary pain condition, but other painful conditions are not allowed due to a significant confounding effect on the study. Concurrent knee interventions, such as injections, have different expected time courses of treatment effects. The exclusion criteria timepoints for each intervention are meant to enroll participants at a relatively stable periods of time after the interventions, so that pain and function do not change dramatically across Study Visits.

Description

Inclusion Criteria:

• Knee pain for greater than 6 months.
• Moderate-to-severe knee pain (>3/10) due to osteoarthritis, as defined by American College of Rheumatology and EULAR diagnostic criteria, on >50% of days in the past month.
• KL grade 2-4 indicating significant degenerative changes on knee X-ray.
• 45-80 years old

Exclusion Criteria:

• Inflammatory arthritis (e.g. rheumatoid arthritis).
• More intense pain due to another chronic pain syndrome (e.g. fibromyalgia, hip osteoarthritis)
• Significant pain or weakness in the lower extremities due to a neurological condition (e.g. lumbar radiculopathy, paresis due to stroke)
• Acute pain that is more intense than knee osteoarthritis pain
• Current routine use of more than 15 mg oral morphine equivalents per day (use of <15 mg OME does not exclude the participant).
• Recent new medication, exercise, behavioral, or complementary and integrative treatment started in the last month. Stable use of these treatments for greater than 1 month does not exclude the participant.
• Recent intra-articular injection of steroid or other agent (greater than 1 month does not exclude the participant)
• Recent knee radiofrequency ablation (greater than 3 months does not exclude the participant)
• Recent knee arthroscopic surgery (greater than 3 months does not exclude the participant)
• History of knee replacement or open knee surgery on the index knee, defined as the more painful knee on average over the last month.
• Inability to walk or climb stairs without significant assistance (e.g. a one-person assist, use a wheel chair; however, the use of a cane does not exclude the participant).
• Inability to participate in study procedures (e.g. cognitive impairment limiting ability to understand directions, inability to understand and read English)
• Uncontrolled or unstable medical disorder preventing participation in study procedures
• History of brain surgery
• Tattoos on sensory testing sites
• Pregnancy
• Breastfeeding
• Inability to under knee MRI scan due to incompatible devices or foreign bodies.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Chronic knee pain with knee osteoarthritis; Adults 45-80 years old who have moderately severe knee osteoarthritis. They must have experienced knee pain for greater than 6 months and rate their daily knee pain at >3 on a 0-10 numeric rating scale.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
6 minute walk test pain intensity	Pain intensity on numeric rating scale (0-10) during and around the time of the 6-minute walk test.	6 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Distance walked in the 6-minute walking test	Distance walked during 6 minute walking task	6 minutes

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quantitative sensory testing	Responses to quantitative sensory tests that assess sensation of painful and non-painful stimuli. The stimuli are calibrated and carefully controlled with safety measures to prevent tissue damage.	2-3 hours
Physical function performance and pain	A battery of standardized physical function tests including a stair climb test, fast-paced walk test, balance test, and sit-to-stand test, will be done to measure physical performance. Outcome measurements include the time to complete the test, distance walked, and number of repetitions. Pain intensity is reported on the numeric rating scale (0-10) during this battery of tests.	2-3 hours
Brain imaging	Brain activity will be measured non-invasively using functional near-infrared spectroscopy	2-3 hours
Biomechanics during physical activity	Aspects of body movement will be measured non-invasively during physical performance tests, including the 6-minute walk test	3-4 hours
Multidimensional pain assessment	Multidimensional aspects of chronic pain will be measured through written surveys and a semi-structured clinical evaluation.	1 hour
Knee MRI	Structural changes of the knee will be measured, including the use of standard scoring systems.	1 hour

Collaborators and Investigators

• Sponsor: University of Pittsburgh
• Collaborators: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
• Investigators: Principal Investigator: Benedict Alter, MD, PhD, University of Pittsburgh

Study record dates

Study Major Dates

• Study Start (Actual): January 7, 2026
• Primary Completion (Estimated): August 1, 2030
• Study Completion (Estimated): August 1, 2030

Study Registration Dates

• First Submitted: December 26, 2025
• First Submitted That Met QC Criteria: December 26, 2025
• First Posted (Actual): December 30, 2025

Study Record Updates

• Last Update Posted (Actual): January 29, 2026
• Last Update Submitted That Met QC Criteria: January 27, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Musculoskeletal Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Osteoarthritis; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Osteoarthritis, Knee; Chronic Pain
• Other Study ID Numbers: STUDY25080027; 1R01AR086796-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD will be shared in accordance with NIH HEAL regulatory requirements.
• IPD Sharing Time Frame: IPD will be shared in accordance with NIH HEAL requirements, meaning that IPD will be made publicly available after the publication of results.
• IPD Sharing Access Criteria: IPD will be publicly available.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No