Clinical trial NCT06419439: Ketamine-assisted Integrative Treatment for Veterans With Chronic Low Back Pain and Comorbid Depression
Official title: Ketamine-assisted Integrative Treatment for Veterans With Chronic Low Back Pain and Comorbid Depression
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Chronic Low Back Pain
Depression
Keywords: Feasibility Studies
Pilot Projects
Randomized Controlled Trials
Clinical trials
Psychosocial Intervention
Narrative Medicine
Narrative Therapy
Ketamine
Ketamine, therapeutic use
Veterans
Veterans, Research Subjects
Low Back Pain, Recurrent/Chronic
Depression
Hallucinogens, Therapeutic Use
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
First posted: 2024-05-17
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: This study will occur in two phases which will occur sequentially and have different designs. The initial phase is a single-arm open-label, nonrandomized, non-blinded pilot study (n=5). The objective is to develop and assess initial feasibility of study procedures and obtain participant feedback through semi-structured exit interviews. The subsequent phase, informed by these findings, will consist 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.
Primary purpose: OTHER

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.

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.
* Previously experienced serious adverse effects with ketamine.
* On day of ketamine infusions, a urine drug screen positive for non-prescribed substances(s) (except cannabis) will exclude a participant from receiving ketamine
* Current or previous abuse of ketamine.

Primary outcomes:
measure: Pain Interference (PROMIS Short Form v1.1 Pain Interference 6b)
timeFrame: Visit 7 (8-10 days post randomization)
Secondary outcomes:
measure: Pain intensity (Numeric Rating Scale)
timeFrame: Visit 7 (8-10 days post randomization)
measure: Depression (Quick Inventory of Depressive Symptoms - Self Report (QIDS-SR) )
timeFrame: Visit 7 (8-10 days post randomization)
Other outcomes:
measure: Feasibility - Enrollment
timeFrame: 18 months from start of study
measure: Presence of adverse events (AE)s
timeFrame: Visits 1-7 or weekly (whichever is more frequent); Visit 8 (1 month follow up), Visit 9 (3 month follow up)
measure: Pain Interference (PROMIS Short Form v1.1 Pain Interference 6b)
timeFrame: Visit 1 (Baseline), Visit 5 (post ketamine pre randomization), Visit 8 (1 month follow up), Visit 9 (3 month follow up)
measure: Pain Intensity (Numeric Rating Scale)
timeFrame: Visit 1 (Baseline), Visit 5 (post ketamine pre randomization), Visit 8 (1 month follow up), Visit 9 (3 month follow up)
measure: Depression (Quick Inventory of Depressive Symptoms - Self Report (QIDS-SR) )
timeFrame: Visit 1 (Baseline), Visit 5 (post ketamine pre randomization), Visit 8 (1 month follow up), Visit 9 (3 month follow up)
measure: Acceptability
timeFrame: Visit 7 (8-10 days post randomization)
measure: Global Impression of Change (Patient Global Impression of Change (PGIC))
timeFrame: Visit 7 (8-10 days post randomization), Visit 8 (1 month follow up), Visit 9 (3 month follow up)
measure: Cognitive Flexibility (Cognitive Flexibility Scale (CFS))
timeFrame: Visit 1 (Baseline) , Visit 5 (post ketamine infusions pre randomization), Visit 7 (8-10 days post randomization), Visit 8 (1 month follow up), Visit 9 (3 month follow up)
measure: Psychological Flexibility (Emotion Regulation Questionnaire (ERQ-9))
timeFrame: Visit 1 (Baseline) , Visit 5 (post ketamine infusions pre randomization), Visit 7 (8-10 days post randomization), Visit 8 (1 month follow up), Visit 9 (3 month follow up)
measure: Psychological Inflexibility (Acceptance and Action Questionnaire-II (AAQII))
timeFrame: Visit 1 (Baseline) , Visit 5 (post ketamine infusions pre randomization), Visit 7 (8-10 days post randomization), Visit 8 (1 month follow up), Visit 9 (3 month follow up)
measure: Psychologically insightful experiences occurring in response to ketamine administration (Psychological Insight Questionnaire (PIQ))
timeFrame: Visit 5 (post ketamine infusions pre randomization)
measure: Mystical Experiences Occasioned by Ketamine (Mystical Experience Questionnaire (MEQ))
timeFrame: Visit 5 (post ketamine infusions pre randomization)
measure: Catastrophizing (Catastrophizing Subscale from the Coping Strategies Questionnaire (CSQ-CAT))
timeFrame: Visit 1 (Baseline) , Visit 5 (post ketamine infusions pre randomization), Visit 7 (8-10 days post randomization), Visit 8 (1 month follow up), Visit 9 (3 month follow up)
measure: Self-Efficacy (PROMIS Self-Efficacy for Chronic Conditions - Managing Daily Activities -Short Form 4a)
timeFrame: Visit 1 (Baseline) , Visit 5 (post ketamine infusions pre randomization), Visit 7 (8-10 days post randomization), Visit 8 (1 month follow up), Visit 9 (3 month follow up)
measure: Fear-Avoidance Beliefs/Kinesiophobia (Fear-Avoidance Beliefs Questionnaire-Physical Activity Subscale (FABQ-PA))
timeFrame: Visit 1 (Baseline) , Visit 5 (post ketamine infusions pre randomization), Visit 7 (8-10 days post randomization), Visit 8 (1 month follow up), Visit 9 (3 month follow up)
measure: Nociplastic Pain Characteristics (Fibromyalgia Survey Questionnaire (FSQ))
timeFrame: Visit 1 (Baseline)
measure: Neuropathic Pain Characteristics (painDETECT)
timeFrame: Visit 1 (Baseline)
measure: Feasibility - retention/attendance
timeFrame: Visit 7 (8-10 days post randomization)
measure: Feasibility - measurement completion
timeFrame: Visit 9 (3 month follow up)
Locations:
city: Ann Arbor
country: United States
facility: VA Ann Arbor Healthcare System, Ann Arbor, MI
state: Michigan
Study officials:
affiliation: VA Ann Arbor Healthcare System, Ann Arbor, MI
name: Victoria D Powell, MD
role: PRINCIPAL_INVESTIGATOR
References: