Chronic Pain After Combat-Related Traumatic Brain Injury (cTBI-Pain Study) A Prospective Cohort Study of Pain Chronification After Combat-Related Traumatic Brain Injury (TBI-Pain)

Combat-related traumatic brain injury (cTBI), particularly blast-related injury, is frequently associated with the development of persistent and disabling chronic pain. This prospective observational cohort study aims to determine the incidence, phenotypes, and early predictors of chronic pain following mild to moderate combat-related TBI. Adults will be enrolled within 14 days of injury and followed for 6 months. The primary endpoint is clinically significant chronic pain at 3 months, defined by pain intensity and functional interference. The study will evaluate clinical, psychological, and physiological factors to develop and internally validate a prognostic model for chronic pain risk after cTBI.

Study Overview

• Status: Not yet recruiting
• Conditions: Pain; Chronic Pain; Chronic Pain Due to Injury

Detailed Description

Combat-related traumatic brain injury (cTBI), particularly blast-associated injury, is a major contributor to the development of chronic pain syndromes in military populations. Pain following cTBI may present as chronic post-traumatic headache, cervicogenic pain, neuropathic pain, or widespread pain associated with central sensitization. The interaction between neuronal injury, psychological stress (including PTSD), sleep disturbance, and associated peripheral trauma creates a high-risk environment for pain chronification.

This prospective observational cohort study will enroll adults with mild to moderate combat-related traumatic brain injury within 14 days of injury. Participants will undergo standardized clinical, psychometric, and physiological assessments during the acute phase and will be followed longitudinally at 6 weeks, 3 months, and 6 months.

Pain intensity will be assessed using the Numerical Rating Scale (NRS) and the Brief Pain Inventory (BPI). Neuropathic pain features will be evaluated using DN4, and central sensitization symptoms using the Central Sensitization Inventory (CSI). Psychological factors including PTSD (PCL-5), depression (PHQ-9), anxiety (GAD-7), and pain catastrophizing (PCS) will be assessed. Sleep disturbance will be evaluated using the Insomnia Severity Index (ISI). Functional outcomes will be measured using WHODAS 2.0 and PROMIS Physical Function. A subgroup of participants will undergo physiological testing, including heart rate variability (HRV) and quantitative sensory testing (QST).

The primary endpoint is clinically significant chronic pain at 3 months, defined as NRS ≥4 and/or BPI interference score ≥4. Secondary outcomes include neuropathic pain phenotype, functional impairment, psychological outcomes, and persistent analgesic use at 6 months.

Multivariable regression modeling, including logistic regression and penalized methods (LASSO), will be used to identify independent predictors of chronic pain. Internal validation will be performed using bootstrapping techniques. Model performance will be evaluated using ROC-AUC and calibration metrics.

The study aims to develop a clinically applicable risk prediction model to identify individuals at high risk for chronic pain following combat-related TBI and to inform early preventive and rehabilitative interventions.

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Dmytro Dmytriiev, PhD.Professor; Phone Number: +380674309449; Email: d.dmytriiev@superhumans.com

Study Locations

• Ukraine
  • Lviv, Ukraine
    • Superhumans War Trauma Center

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Adults aged 18-60 years with mild to moderate combat-related traumatic brain injury (blast, impact, or combined mechanism) presenting to participating trauma and rehabilitation centers in Ukraine. Participants will be enrolled within 14 days of injury and followed prospectively for 6 months to assess the development of chronic pain and related psychological and functional outcomes.

Description

Inclusion Criteria:

• Age 18 to 60 years
• Combat-related traumatic brain injury (blast, impact, or combined mechanism)
• Mild to moderate traumatic brain injury
• Enrollment within 14 days after injury
• Ability to provide written informed consent

Exclusion Criteria:

• Severe traumatic brain injury with prolonged impaired consciousness
• Pre-existing severe psychiatric disorder unrelated to trauma
• Chronic pain condition predating the traumatic brain injury
• Inability to complete follow-up assessments
• Severe medical condition limiting participation

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Combat-Related TBI Cohort; Adults aged 18-60 years with mild to moderate combat-related traumatic brain injury enrolled within 14 days of injury. Participants will undergo standardized clinical, psychological, and pain assessments and will be followed prospectively for 6 months to evaluate the development of chronic pain.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinically significant chronic pain at 3 months after injury.	Clinically significant chronic pain is defined as pain intensity ≥4 on the 0-10 Numerical Rating Scale (NRS) and/or pain interference score ≥4 on the Brief Pain Inventory (BPI) at 3 months post-injury. The proportion of participants meeting this definition will be calculated, and predictors of chronic pain will be evaluated using multivariable modeling.	From injury to 3 months (±2 weeks) post-injury.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinically significant chronic pain at 6 months	Presence of chronic pain defined as NRS ≥4 and/or BPI interference score ≥4 at 6 months post-injury.	6 months (±3 weeks) after injury
Neuropathic pain phenotype	Presence of neuropathic pain features defined as DN4 score ≥4.	3 and 6 months after injury

Collaborators and Investigators

• Sponsor: Charitable Organisation Charitable Fund Superhumans (Co Cf Superhumans)

Study record dates

Study Major Dates

• Study Start (Estimated): February 15, 2026
• Primary Completion (Estimated): February 15, 2026
• Study Completion (Estimated): December 15, 2026

Study Registration Dates

• First Submitted: February 14, 2026
• First Submitted That Met QC Criteria: February 14, 2026
• First Posted (Actual): February 20, 2026

Study Record Updates

• Last Update Posted (Actual): February 24, 2026
• Last Update Submitted That Met QC Criteria: February 22, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Chronic pain; Neuropathic pain; Sleep disturbance; Blast injury; Pain prediction; Combat-related traumatic brain injury; cTBI; Military trauma
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Mental Disorders; Wounds and Injuries; Neuromuscular Diseases; Peripheral Nervous System Diseases; Sleep Wake Disorders; Barotrauma; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Pain; Parasomnias; Chronic Pain; Neuralgia; Blast Injuries
• Other Study ID Numbers: 09v313022026

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data (IPD) will not be publicly posted due to privacy considerations related to military trauma data. De-identified data may be made available upon reasonable request, subject to approval by the study steering committee and execution of a data use agreement.

Drug and device information, study documents

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