KALM-B: Ketamine-assisted Psychotherapy (KAP) to Lessen Morbidity After Burn Injury

Обзор

A study looking at the safety and tolerability of KAP (Ketamine-Assisted Psychotherapy) in the burn population.

Подробное описание

BACKGROUND AND RATIONALE Burn injuries are among the most devastating forms of trauma, often resulting in significant physical pain and long-term psychological distress. Survivors frequently experience acute stress disorder (ASD), which may progress to post-traumatic stress disorder (PTSD), depression, anxiety, and chronic opioid dependence. PTSD has been documented in up to 45% of military burn survivors and approximately one-third of civilians with severe burn trauma. Despite improvements in surgical and rehabilitative care, the psychological sequelae of burn injuries remain under-recognized and under-treated.

The immediate post-injury period is marked by elevated stress and emotional dysregulation, yet access to timely, structured mental health interventions is limited. Traditional approaches often fail to reach patients during this critical window. At the University of Utah Burn Center, which treats over 450 inpatients and 6,500 outpatients annually, there is an urgent need for feasible and scalable approaches to address psychological distress early in the recovery process.

Ketamine-assisted psychotherapy (KAP) combines the administration of ketamine, a dissociative anesthetic with well-documented rapid-onset antidepressant properties, with psychotherapeutic support in a controlled clinical environment. KAP has shown potential in other trauma-affected populations and is being explored for its ability to support emotional processing, reduce distress, and potentially interrupt the progression from acute stress to more persistent mental health disorders. However, its use in the context of acute burn injury has not been systematically evaluated.

The KALM-B Study (Ketamine-Assisted Therapy to Lessen Morbidity after Burn Injury) is a pilot project designed to assess the safety and feasibility of implementing KAP in recently burned patients with acute stress symptoms. The study will recruit 12 adult patients who screen positive for acute stress symptoms during their hospitalization and offer participation in up to two KAP sessions following discharge, delivered in partnership with the Huntsman Mental Health Institute.

The primary objective is to evaluate the safety and tolerability of KAP after burn and the feasibility of recruitment, enrollment, and completion of the study intervention. Secondary objectives include assessing the safety and tolerability of KAP in this unique patient population. Exploratory objectives will descriptively assess changes in symptoms of acute stress, anxiety, depression, and opioid use through 6 months post-intervention.

This study represents a first step toward understanding how novel trauma-informed interventions might be integrated into early burn care. By characterizing feasibility, safety, and symptom trends over time, KALM-B will provide foundational data to inform future research and potential care models aimed at supporting psychological recovery after burn injury.

Вмешательства

• Поведенческое Preparatory Session
  A preparatory session will be completed with the subject by a trained psychotherapist to prepare them for the 1st Ketamine treatment
• Препарат Ketamine-assisted Psychotherapy Session #1
  Ketamine will be administered intra-muscularly at a starting dose of 0.5 mg/kg and can be titrated up to 1.0 mg/kg, to a maximum of 60 mg, based on patient response. The first study intervention for KAP will include a preparatory session a 2.5-3 hour therapy session.
• Препарат Ketamine-assisted Psychotherapy Session #2
  The second study intervention for KAP will include a 2.5-3 hour therapy session.
• Поведенческое Integration Session
  An integration session will be held with a trained psychotherapist after the 2nd Ketamine administration

Первичные конечные точки

• Safety and Tolerability defined by the number of participants with treatment-related adverse events [Срок оценки: From baseline through 6 months post-treatment follow-up (assessments at 1, 3, and 6 months)]

Вторичные конечные точки (9)

• Feasibility - Recruitment rate [Срок оценки: From study opening to completion of recruitment, up to 24 months]
• Feasibility - Treatment Completion Rate [Срок оценки: From enrollment through completion of all scheduled KAP sessions, assessed up to 12 weeks]
• Feasibility - Follow-up Completion Rate [Срок оценки: From baseline through 6 months post-treatment follow-up (assessments at 1, 3, and 6 months)]
• Timeliness of Intervention Delivery [Срок оценки: Baseline (from injury to initiation of treatment; up to 12 months)]
• Opioid Use [Срок оценки: From baseline through 6 months post-treatment follow-up (assessments at 1, 3, and 6 months)]
• Acute Stress Symptoms based on National Stressful Events Survey Acute Stress Disorder Short Scale (NSESSS) [Срок оценки: From baseline through 6 months post-treatment follow-up (assessments at 1, 3, and 6 months)]
• Incidence of PTSD based on PTSD Checklist for DSM-5 (PCL-5) [Срок оценки: From baseline through 6 months post-treatment follow-up (assessments at 1, 3, and 6 months)]
• Anxiety Symptoms based on the Generalized Anxiety Disorder 7-item scale [Срок оценки: From baseline through 6 months post-treatment follow-up (assessments at 1, 3, and 6 months)]
• Depressive Symptoms based on Patient Health Questionnaire-9 Screening tool [Срок оценки: From baseline through 6 months post-treatment follow-up (assessments at 1, 3, and 6 months)]

Критерии участия

Критерии включения

• Subjects 18 - 65 yrs with > 15 % Total Body Surface Area Burns.
• National Stressful Events Survey Acute Stress Disorder Short Scale (NSESSS) average total score>= 2 (severity scale of none (0), mild (1), moderate (2), severe (3), or extreme (4) ) prior to discharge from UUH.

Критерии исключения

• Allergy or previous adverse reactions to ketamine
• Pending surgical interventions
• Active systemic infection, sepsis, or hemodynamic instability
• Physical limitations from burn injury that preclude safe travel to outpatient visits or positioning for therapy.
• Lack of reliable transportation, caregiver support, or housing stability.
• Language barrier
• Personal history or first- or second-degree relatives with schizophrenia, bipolar affective disorder, delusional disorder, schizoaffective disorder, psychosis, or other psychotic spectrum illness.
• Currently meeting DSM-5 criteria for Dissociative Disorder, or other psychiatric conditions judged to be incompatible with the establishment of rapport or safe exposure to ketamine.
• Currently meeting DSM-5 criteria for Cluster B Personality Disorder.
• Severe depression requiring immediate standard-of-care treatment (e.g., hospitalization).
• Suicidal ideation over the past month as assessed as a yes to question 3, 4, or 5 on the Columbia-Suicide Severity Rating Scale, Suicidal Ideation section
• Current or prior history of PTSD diagnosis
• Current or history within the last two years of meeting DSM-V criteria of substance use disorder (excluding caffeine and nicotine).
• Current substance use disorders may be identified through the drug urine screening test or undergoing treatment (methadone/Suboxone) .
• Congestive heart failure, including all New York Heart Association Classes.
• Angina pectoris, cardiac hypertrophy, cardiac ischemia, myocardial infarction
• Uncontrolled hypertension at the time of enrollment (BP>140 systolic or 90 diastolic), coronary artery disease, artificial heart valve
• Prolonged or congenital long QT syndrome (>450 ms), serious cardiac arrhythmias, tachycardia, a clinically significant screening ECG abnormality
• History of hypersensitivity to ketamine
• Receiving ketamine treatments for psychiatric condition within the past 6 months
• Seizure disorder
• Moderate to severe dementia
• History of significant traumatic brain injury
• Requires the use of supplemental oxygen.
• Require Propranolol for Burn Hypermetabolism
• Any other condition that would, in the Investigator's judgment, contraindicate the subject's participation in the clinical study due to safety concerns or compliance with clinical study procedures (e.g., infection/inflammation, intestinal obstruction, unable to swallow medication, \[patients may not receive the drug through a feeding tube\], social/ psychological issues, etc.)
• Subjects taking prohibited medications. A washout period of prohibited medications for a period of at least five half-lives should occur prior to study registration. These medications include antipsychotic medications, doses of benzodiazepines in excess of 20mg diazepam equivalents per day.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• University of Utah Health — Salt Lake City

Публикации

• Fava M, Freeman MP, Flynn M, Judge H, Hoeppner BB, Cusin C, Ionescu DF, Mathew SJ, Chang LC, Iosifescu DV, Murrough J, Debattista C, Schatzberg AF, Trivedi MH, Jha MK, Sanacora G, Wilkinson ST, Papakostas GI. Double-blind, placebo-controlled, dose-ranging trial of intravenous ketamine as adjunctive therapy in treatment-resistant depression (TRD). Mol Psychiatry. 2020 Jul;25(7):1592-1603. doi: 10.1 PMID 30283029
• Singh JB, Fedgchin M, Daly EJ, De Boer P, Cooper K, Lim P, Pinter C, Murrough JW, Sanacora G, Shelton RC, Kurian B, Winokur A, Fava M, Manji H, Drevets WC, Van Nueten L. A Double-Blind, Randomized, Placebo-Controlled, Dose-Frequency Study of Intravenous Ketamine in Patients With Treatment-Resistant Depression. Am J Psychiatry. 2016 Aug 1;173(8):816-26. doi: 10.1176/appi.ajp.2016.16010037. Epub 201 PMID 27056608
• Castellanos JP, Woolley C, Bruno KA, Zeidan F, Halberstadt A, Furnish T. Chronic pain and psychedelics: a review and proposed mechanism of action. Reg Anesth Pain Med. 2020 Jul;45(7):486-494. doi: 10.1136/rapm-2020-101273. Epub 2020 May 4. PMID 32371500
• Le Cornec C, Le Pottier M, Broch H, Marguinaud Tixier A, Rousseau E, Laribi S, Janiere C, Brenckmann V, Guillerm A, Deciron F, Kabbaj A, Jenvrin J, Pere M, Montassier E. Ketamine Compared With Morphine for Out-of-Hospital Analgesia for Patients With Traumatic Pain: A Randomized Clinical Trial. JAMA Netw Open. 2024 Jan 2;7(1):e2352844. doi: 10.1001/jamanetworkopen.2023.52844. PMID 38285446
• Du R, Han R, Niu K, Xu J, Zhao Z, Lu G, Shang Y. The Multivariate Effect of Ketamine on PTSD: Systematic Review and Meta-Analysis. Front Psychiatry. 2022 Mar 9;13:813103. doi: 10.3389/fpsyt.2022.813103. eCollection 2022. PMID 35356723
• Fremont R, Brown O, Feder A, Murrough J. Ketamine for Treatment of Posttraumatic Stress Disorder: State of the Field. Focus (Am Psychiatr Publ). 2023 Jul;21(3):257-265. doi: 10.1176/appi.focus.20230006. Epub 2023 Jun 28. PMID 37404968
• Romanowski KS, Carson J, Pape K, Bernal E, Sharar S, Wiechman S, Carter D, Liu YM, Nitzschke S, Bhalla P, Litt J, Przkora R, Friedman B, Popiak S, Jeng J, Ryan CM, Joe V. American Burn Association Guidelines on the Management of Acute Pain in the Adult Burn Patient: A Review of the Literature, a Compilation of Expert Opinion, and Next Steps. J Burn Care Res. 2020 Nov 30;41(6):1129-1151. doi: 10.10 PMID 32885244
• Stojanovic M, Marinkovic M, Milicic B, Stojicic M, Jovic M, Jovanovic M, Isakovic Subotic J, Jurisic M, Karamarkovic M, Dekic A, Radenovic K, Mihaljevic J, Radosavljevic I, Sudecki B, Savic M, Kostic M, Garabinovic Z, Jeremic J. The Role of Ketamine as a Component of Multimodal Analgesia in Burns: A Retrospective Observational Study. J Clin Med. 2024 Jan 29;13(3):764. doi: 10.3390/jcm13030764. PMID 38337458

Идентификаторы

NCT: NCT07563296 · 192679

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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