Connectivity Changes Associated With Ketamine Assisted Psychotherapy for PTSD

Study Overview
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Brief Summary
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The goal of this clinical trial is to learn about the effects of Ketamine Assisted Psychotherapy [KAP] on individuals with Post Traumatic Stress Disorder [PTSD]. The main questions it aims to answer are: Does KAP improve symptoms of PTSD? What changes in brain network connectivity are seen with KAP?

Detailed Description
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A total of 14 adult patients with PTSD will be recruited from UNM outpatient clinics and undergo rsfMRI and behavioral assessment prior to ketamine treatment. They will complete baseline scan at day one, a preparatory session (initial part of KAP), IM ketamine treatment, then within 24 hours, an integration session to take advantage of neuroplasticity for optimal therapeutic progress. Each participant will have two complete KAP sessions (preparation, treatment, and integration) followed by rsfMRI within approximately 24 hours, and again approximately two weeks after the completion of the second KAP session. Patients will also have repeat clinical assessments after each treatment. Changes in PTSD symptoms will be correlated with changes in connectivity at each rsfMRI.

Official Title
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Connectivity Changes Associated With Ketamine Assisted Psychotherapy for PTSD

Conditions
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PTSD

Intervention / Treatment
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* Drug: Ketamine Hydrochloride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants may be eligible for enrollment if all the following inclusion criteria apply within the thirty days prior to first ketamine administration session: Between the ages of 18 to 65 years old. Meet DSM-5 criteria for Port-Traumatic Stress Disorder [PTSD] based on clinical interview. Able to provide informed consent. Are proficient in reading and speaking English. Agree to refrain from using stimulants during the day of the medication session. Agree to refrain from alcohol and cannabis for 24 hours before and the day of medication session. Subjects taking other psychotropic medications (e.g. anti-depressants, anxiolytics, methadone, buprenorphine, naltrexone) must be maintained on a stable dose for at least four weeks before study initiation. Agree to not operate a car or any other heavy equipment for the rest of the day after the ketamine administration. If necessary, are willing to be contacted via telephone on a daily basis by the therapist or team after each experiential session. Able to identify one or two caregiver support persons who can drive participant home, stay with them overnight, be reached by the team, and provide collateral information as needed. Willing to inform the investigator within 48 hours if any medical conditions occur or procedures are planned. Exclusion Criteria: Participants will be excluded from the study if any of the following criteria apply: They are considered an immediate suicide risk by clinician assessment or felt to be likely to require hospitalization during the study. Have had a psychiatric or medical hospitalization, or an Emergency Department visit, within four weeks of the study entry. Subjects who meet DSM-5 criteria for current bipolar disorder based on clinical interview. Subjects who meet DSM-5 criteria for current or history of psychotic spectrum disorders based on clinical interview. Subjects meeting DSM-5 criteria for current substance use disorder (i.e., not in early or sustained remission) other than tobacco use disorder. Subjects who report use of ketamine >20 times in the past or who meet DSM-5 criteria for Other Hallucinogen Use Disorder due to ketamine use including subjects who are currently in early or sustained remission. Women who are pregnant or nursing, and women who do not consent to use methods of highly effective birth control during the study. Subjects with hypertension as defined by a baseline visit systolic blood pressure (SBP) >140 mmHg or a diastolic blood pressure (DBP) >90 mmHg. A history of allergic or other adverse reaction to ketamine (or its excipients). Clinically significant physical exam findings or self-reported medical conditions for which a transient increase in blood pressure could be significantly detrimental (e.g. glaucoma, aneurysmal disease, cardiovascular disease, or end-stage renal disease). QTc will be measured in all subjects and those with QTc 450ms or longer will be excluded. High risk of adverse emotional or behavioral reaction based on investigator's clinical evaluation (e.g., evidence of serious personality disorder, antisocial behavior, serious current stressors, lack of meaningful social support). Documented evidence of significant renal or hepatic dysfunction at screening. Significantly impaired liver function is defined as 1) Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) > 5 × upper limit of normal (ULN); 2) ALT or AST > 3 × ULN with concomitant total bilirubin > 2.0 × ULN; or 3) ALT or AST ≥ 3 × ULN with the appearance of fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever, rash, and/or eosinophilia. Blood pressure will be monitored at all subsequent visits, and participants will receive study medication only if blood pressure is less than or equal to 140 systolic, 90 diastolic at safety screening on the day of the drug administration sessions.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: This is a single arm, open-label, prospective cohort clinical trial. No blinding is required for this trial. A total of 14 adult patients with PTSD will be recruited from UNM outpatient clinics and undergo rsfMRI and behavioral assessment prior to ketamine treatment. They will complete baseline scan at day one, a preparatory session (initial part of KAP), IM ketamine treatment, then within 24 hours, an integration session to take advantage of neuroplasticity for optimal therapeutic progress. Each participant will have two complete KAP sessions (preparation, treatment, and integration) followed by rsfMRI within approximately 24 hours, and again approximately two weeks after the completion of the second KAP session. Patients will also have repeat clinical assessments after each treatment. Changes in PTSD symptoms will be correlated with changes in connectivity at each rsfMRI.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ketamine Assisted Psychotherapy [KAP]<br>A total of 14 adult patients with PTSD will be recruited from UNM outpatient clinics and undergo rsfMRI and behavioral assessment prior to ketamine treatment. They will complete baseline scan at day one, a preparatory session (initial part of KAP), IM ketamine treatment, then within 24 hours, an integration session to take advantage of neuroplasticity for optimal therapeutic progress. Each participant will have two complete KAP sessions (preparation, treatment, and integration) followed by rsfMRI within approximately 24 hours, and again approximately two weeks after the completion of the second KAP session. Patients will also have repeat clinical assessments after each treatment. Changes in PTSD symptoms will be correlated with changes in connectivity at each rsfMRI. | Drug: Ketamine Hydrochloride<br>* This is a single arm, open-label, prospective cohort clinical trial. No blinding is required for this trial. A total of 14 adult patients with PTSD will be recruited from UNM outpatient clinics and undergo rsfMRI and behavioral assessment prior to ketamine treatment. They will complete baseline scan at day one, a preparatory session (initial part of KAP), IM ketamine treatment, then within 24 hours, an integration session to take advantage of neuroplasticity for optimal therapeutic progress. Each participant will have two complete KAP sessions (preparation, treatment, and integration) followed by rsfMRI within approximately 24 hours, and again approximately two weeks after the completion of the second KAP session. Patients will also have repeat clinical assessments after each treatment. Changes in PTSD symptoms will be correlated with changes in connectivity at each rsfMRI.<br>* Other names: KAP;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical outcome: PTSD severity | as defined by change in score on Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) following KAP treatments (Assessment Visit 3) compared to baseline (Assessment Visit 1). | 14-21 days | 
| Imaging Outcome: Changes in functional connectivity | change in the functional connectivity between vmPFC and amygdala from Baseline to Assessment Visit 4 as measured by fMRI. | 28-35 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Depression severity | Improvement in depression, as indicated by reduced Montgomery-Asberg Depression Rating Scale (MADRS), following KAP treatments (Assessment Visit 3) compared to baseline (Assessment Visit 1). | 14-21 days | 
| Persisting PTSD effect | The changes in score on Clinician-Administered PTSD Scale for DSM-5 (CAPS-5). | 28-35 days | 
| Correlation of clinical and imaging outcomes | Change in connectivity between the vmPFC and amygdala from Assessment Visit 1 to Assessment Visit 4 with degree of PTSD symptom change. | 28-35 days | 
| Persisting MDD effect | Concurrent MDD (MADRS) will persist at last evaluation two weeks after completion of active treatment. | 28-35 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PTSD, Ketamine Assisted Psychotherapy, Brain network connectivity