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Clinical Trials/NCT06419439
NCT06419439
Recruiting
Phase 2

Ketamine-assisted Integrative Treatment for Veterans With Chronic Low Back Pain and Comorbid Depression

VA Office of Research and Development1 site in 1 country44 target enrollmentDecember 3, 2025

Overview

Phase
Phase 2
Intervention
Ketamine hydrochloride
Conditions
Chronic Low Back Pain
Sponsor
VA Office of Research and Development
Enrollment
44
Locations
1
Primary Endpoint
Pain Interference (PROMIS Short Form v1.1 Pain Interference 6b)
Status
Recruiting
Last Updated
4 months ago

Overview

Brief Summary

This is a pilot study to evaluate the feasibility, acceptability, and safety of ketamine infusions followed by a brief behavioral intervention in Veterans with chronic low back pain and depression.

Detailed Description

Chronic low back pain (CLBP) and depression are top causes of disability in the United States. Veterans are more likely to have both; prevalence is increasing. When CLBP and depression occur together, patients report more functional limitations, unemployment, and higher healthcare spending, and treatment is less successful. Novel approaches simultaneously addressing pain interference and depression symptoms are needed. This study will involve initial pilot feasibility testing of an intervention designed to help participants with chronic low back pain and depression both reduce pain interference and improve mood. This study will occur in two phases. The initial phase is a open-label single-arm pilot of the combined intervention (ketamine infusions followed by the brief behavioral intervention) in a small sample of Veterans (n=5). The objective is to develop and assess initial feasibility of study procedures and obtain participant feedback through semi-structured exit interviews. The second phase consists of a single-blind, two-arm, pilot feasibility randomized controlled trial (RCT) (n=44, 22 per arm) which will (a) assess feasibility benchmarks and (b) collect outcome data that will be used to calculate sample size to power a larger RCT.

Registry
clinicaltrials.gov
Start Date
December 3, 2025
End Date
June 30, 2029
Last Updated
4 months ago
Study Type
Interventional
Study Design
Sequential
Sex
All

Investigators

Responsible Party
Sponsor

Eligibility Criteria

Inclusion Criteria

  • Veterans with self-report of moderate to severe, high impact chronic low back pain (defined as 4/10 in severity via NRS, present 3 months on most days) and associated pain interference (defined as T-score 60 on the PROMIS Pain Interference measure), and current significant depressive symptoms (defined as a score 11 on the Quick Inventory of Depressive Symptoms - Self Report (QIDS-SR).
  • Medically stable (no hospitalizations in the past month lasting 3 days).
  • No changes in pain or depression medication regimen in 4 weeks.
  • No planned surgery, injections, hospitalizations, or other new interventions for back pain (except for physical therapy or exercise) or depression during the next four months (study duration).
  • Participants must have an adult who can drive them home after the ketamine treatments.

Exclusion Criteria

  • Inability to speak English due to the narrative intervention being conducted in English.
  • Inability or unwillingness to provide written informed consent (e.g. current delirium).
  • Current psychotic symptoms, or history of schizophrenia, schizoaffective disorder, and other psychotic disorder.
  • Currently participating in another clinical trial for pain or depression.
  • Current uncontrolled hypertension (defined as systolic blood pressure \>160 mmHg and/or diastolic blood pressure \>100 mmHg).
  • Known elevated intracranial pressure, cerebral arterial aneurysm, or elevated intraocular pressure.
  • History of cirrhosis or unstable cardiac condition (e.g., decompensated congestive heart failure).
  • Any of the following lab values \>2x upper limit of normal: alanine transaminase (ALT), aspartate transferase (AST), direct bilirubin, alkaline phosphatase, creatinine; thyroid stimulating hormone (TSH) \<2x lower limit of normal or \>2x upper limit of normal.
  • Positive urine pregnancy test or lack of birth control method in Veterans of childbearing potential.
  • Known hypersensitivity to any excipient in the ketamine injection formulation.

Arms & Interventions

Open label, single arm pilot

Initial phase: A small open-label, single arm pilot study (n=5) will be conducted to develop and assess initial feasibility of study procedures and obtain participant feedback through semi-structured exit interviews. All participants in this open-label single arm pilot will receive the intervention (ketamine infusions followed by the brief behavioral intervention). There will be no control condition, randomization, or blinding.

Intervention: Ketamine hydrochloride

Open label, single arm pilot

Initial phase: A small open-label, single arm pilot study (n=5) will be conducted to develop and assess initial feasibility of study procedures and obtain participant feedback through semi-structured exit interviews. All participants in this open-label single arm pilot will receive the intervention (ketamine infusions followed by the brief behavioral intervention). There will be no control condition, randomization, or blinding.

Intervention: Brief narrative intervention

Intervention + Minimally Enhanced Usual Care

Second phase: Intervention arm of a single-blind, two-arm, pilot feasibility randomized controlled trial (RCT) (n=44, 22 per arm) which will (a) assess feasibility benchmarks and (b) collect outcome data that will be used to calculate sample size to power a larger RCT. Minimally Enhanced Usual Care will consist of educational reading materials regarding chronic back pain and depression.

Intervention: Ketamine hydrochloride

Intervention + Minimally Enhanced Usual Care

Second phase: Intervention arm of a single-blind, two-arm, pilot feasibility randomized controlled trial (RCT) (n=44, 22 per arm) which will (a) assess feasibility benchmarks and (b) collect outcome data that will be used to calculate sample size to power a larger RCT. Minimally Enhanced Usual Care will consist of educational reading materials regarding chronic back pain and depression.

Intervention: Minimally Enhanced Usual Care

Intervention + Minimally Enhanced Usual Care

Second phase: Intervention arm of a single-blind, two-arm, pilot feasibility randomized controlled trial (RCT) (n=44, 22 per arm) which will (a) assess feasibility benchmarks and (b) collect outcome data that will be used to calculate sample size to power a larger RCT. Minimally Enhanced Usual Care will consist of educational reading materials regarding chronic back pain and depression.

Intervention: Brief narrative intervention

Minimally Enhanced Usual Care Only

Second phase: Control arm of a single-blind, two-arm, pilot feasibility randomized controlled trial (RCT) (n=44, 22 per arm) which will (a) assess feasibility benchmarks and (b) collect outcome data that will be used to calculate sample size to power a larger RCT. Minimally Enhanced Usual Care will consist of educational reading materials regarding chronic back pain and depression.

Intervention: Ketamine hydrochloride

Minimally Enhanced Usual Care Only

Second phase: Control arm of a single-blind, two-arm, pilot feasibility randomized controlled trial (RCT) (n=44, 22 per arm) which will (a) assess feasibility benchmarks and (b) collect outcome data that will be used to calculate sample size to power a larger RCT. Minimally Enhanced Usual Care will consist of educational reading materials regarding chronic back pain and depression.

Intervention: Minimally Enhanced Usual Care

Outcomes

Primary Outcomes

Pain Interference (PROMIS Short Form v1.1 Pain Interference 6b)

Time Frame: Visit 7 (8-10 days post randomization)

Pain interference, defined as the extent to which pain impedes enjoyment of and participation in life activities (including cognitive, social, recreational, and self-care activities), will be the primary outcome. Raw scores (range 6 - 30, higher scores indicating more interference) are normed to mean of general population (T-score 50; SD 10); higher T-scores indicate higher pain interference. Minimum clinically important change is 3.0 - 3.5 point reduction in the T-score.

Secondary Outcomes

  • Pain intensity (Numeric Rating Scale)(Visit 7 (8-10 days post randomization))
  • Depression (Quick Inventory of Depressive Symptoms - Self Report (QIDS-SR) )(Visit 7 (8-10 days post randomization))

Study Sites (1)

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