Adding Trauma-focused Psychotherapy to Ketamine Treatment for Chronic PTSD

• Status: Recruiting
• Trial end date: 2025-05-01
• Target enrollment: 0
• Participant gender: All

Summary

The current project will evaluate the efficacy of adding Written Exposure Therapy (WET) to a course of repeated IV ketamine infusions in prolonging PTSD symptom improvement/time to loss of response in patients with chronic PTSD). WET is a brief, 5-session evidence-based written trauma-focused therapy without in between-session assignments, with demonstrated efficacy and low dropout rates in patients with PTSD. WET will be administered to all eligible participants; the first WET sessions will be interleaved with the last two ketamine infusions to take advantage of a window of increased neuroplasticity potentially induced by repeated ketamine infusions. WET will be administered on different days as the ketamine infusions.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Icahn School of Medicine at Mount Sinai
• Treatments: Ketamine

Criteria

Inclusion Criteria:

1. Men or women, 18-70 years of age;

2. Participants must have a level of understanding sufficient to agree to all tests and examinations required by the protocol and must sign a written informed consent document;

3. Participants must fulfill DSM-5 criteria for current civilian or combat-related PTSD, based on clinical assessment by a study psychiatrist and on the CAPS-5, and a past-month total CAPS5 score ≥ 25 at screening - this is done to ensure at least moderate severity and to safeguard against high placebo response rates;

4. Women must be using a medically accepted reliable means of contraception (if using an oral contraceptive medication, they must also be using a barrier contraceptive) or not be of childbearing potential (i.e., surgically sterile, postmenopausal for at least one year);

5. Women of childbearing potential must have a negative pregnancy test at screening and prior to each intravenous infusion;

6. Men who are sexually active with women of childbearing potential must use a medically accepted reliable means of contraception and must agree not to donate sperm for a period of 90 days after receiving the last dose of ketamine;

7. Participants must be able to identify a family member, physician, or friend (i.e. someone who knows them well) who will participate in a Treatment Contract (and e.g. contact the study physician on their behalf in case manic symptoms or suicidal thoughts develop).

Exclusion Criteria:

1. Women who plan to become pregnant, are pregnant or are breast-feeding (because the medical risk of using ketamine during pregnancy and breast-feeding is unknown);

2. Serious, unstable medical illnesses such as hepatic, renal, gastroenterologic, respiratory, cardiovascular, endocrinologic, neurologic, immunologic, or hematologic disease, including gastro-esophageal reflux disease, obstructive sleep apnea, history of difficulty with airway management during previous anesthetics, ischemic heart disease and uncontrolled hypertension, and history of severe head injury;

3. Clinically significant abnormal findings of laboratory parameters, physical examination, or ECG;

4. Renal impairment, as reflected by a BUN >20 mg/dL, and/or creatinine clearance of >1.3 mg/dL;

5. Clinically significant uncorrected hypothyroidism or hyperthyroidism, as indicated by a TSH value 25% above or below the normal range;

6. A Body Mass Index (BMI) >40;

7. Hormonal treatment (e.g., estrogen) started in the 3 months prior to the first infusion day;

8. History of a neurodevelopmental disorder (e.g., autism, pervasive developmental disorder) ;

9. History of one or more seizures without a clear and resolved etiology;

10. Lifetime history of bipolar I or II disorder;

11. Presence of psychotic symptoms, or diagnosis of a lifetime psychotic disorder including schizophrenia or schizoaffective disorder;

12. Drug or alcohol use disorder within the preceding 3 months

13. Previous recreational use of ketamine or PCP on more than one occasion, or any recreational use of ketamine or PCP within the last two years;

14. Previous non-response to clinical or research ketamine or esketamine administration;

15. Current diagnosis of bulimia nervosa or anorexia nervosa;

16. Patients judged clinically to be at serious and imminent suicidal or homicidal risk;

17. SBP >165 and DBP >95 at infusion days - higher BP allowed to account for stress or anxiety;

18. Concurrent treatment with opioid medication, or with long-acting or daytime short-acting benzodiazepines within two weeks of study start;

19. Current cognitive impairment, as defined by a score <23 on the Montreal Cognitive Assessment (MoCA);

20. Estimated IQ <80;

21. Currently receiving evidence-based psychotherapy for PTSD (e.g., prolonged exposure, cognitive processing therapy);

Note: Concurrent treatment with other psychotropic medications (including a short-acting benzodiazepine at bedtime only) will be permitted, but dose must be stabilized for at least three months before study start.