TIMBER Psychotherapy and Ketamine Single Infusion in Chronic PTSD

NCT ID: NCT02766192

Last Updated: 2016-05-09

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-08-31

Brief Summary

Background: The poor prognosis and public health burden of PTSD necessitates the development of more effective and broader treatment approaches. In the etiopathogenesis of PTSD, trauma memories become ingrained into key brain areas through conditioned learning and are triggered by various situations of daily life. The brain glutamate system plays a key role in the process of trauma learning and trauma memories via long-term potentiation. Ketamine administration modulates the glutamate system and has been used in the treatment of depression and PTSD. Previous studies demonstrate that a single low dose of ketamine rapidly improves symptoms of refractory PTSD and treatment resistant depression. Unfortunately the observed response is short-lived (4-7 days, maximum up to 2 weeks) and multiple doses often produce unacceptable side effects. TIMBER (Trauma Interventions using Mindfulness Based Extinction and Reconsolidation for trauma memory) psychotherapy, is a manualized and translational mindfulness based cognitive behavioral therapy specifically designed to target trauma memories and their expressions in PTSD patients. The placebo controlled pilot study examined the efficacy of a protocol combining a single infusion of low dose ketamine (0.5mg/kg) and TIMBER psychotherapy in subjects suffering from chronic PTSD. The objective of this pilot study was to optimize and individualize treatment of chronic PTSD using a rapid, effective, trauma specific, user friendly and inexpensive approach that uses cutting edge psychopharmacological combined with novel psychotherapeutic approaches.

Methodology: The randomized, double blind, placebo-controlled pilot study used a crossover design. Ten subjects with refractory PTSD were assigned to one of two arms: one arm (n=5) received combined ketamine infusion and TIMBER therapy (TIMBER-K arm) and the second (n=5) received combined placebo (normal saline) infusion and TIMBER therapy (TIMBER-P arm). All 10 subjects received a short version of TIMBER therapy after 10 minutes of onset of the infusion in which reactivation of trauma memories was initiated in a controlled manner using standardized scales and scripted narrative of the index trauma. This was followed by a standardized mindfulness based cognitive therapy module to quickly de-escalate the arousal symptoms followed by induction of detached observation and reappraisal of the trauma experience. After completion of the 40-min infusion, all subjects were trained on the full version of TIMBER therapy using methods of mindfulness based graded exposure therapy and a twice-daily schedule of home practice was initiated. The investigators are currently in a process of recruiting fifty more subjects to examine the effects in a larger sample.

Conditions

PTSD

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

TIMBER-Ketamine arm

This arm received TIMBER psychotherapy and ketamine infusion.

Group Type: EXPERIMENTAL

Ketamine

Intervention Type: DRUG

TIMBER Psychotherapy

Intervention Type: BEHAVIORAL

TIMBER-placebo arm

This arm received TIMBER psychotherapy and placebo (normal saline) infusion.

Group Type: PLACEBO_COMPARATOR

TIMBER Psychotherapy

Intervention Type: BEHAVIORAL

Placebo (normal saline)

Intervention Type: DRUG

Interventions

Ketamine

Intervention Type: DRUG

TIMBER Psychotherapy

Intervention Type: BEHAVIORAL

Placebo (normal saline)

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Men or women, 21-60 years of age;

2. Patients attending the outpatient psychiatry clinic of Cooper University Hospital will be screened for this study using DSM-IV diagnostic criteria for PTSD.

3. 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;

4. Participants must fulfill DSM-IV criteria for current civilian or combat-related PTSD, based on clinical assessment by a study psychiatrist, on the self-rated PTSD Check list (PCL-C scores must be at least 51and CAPS score must be at least 50 at screening on the first 17 items of the scale).

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

6. Women of childbearing potential must have a negative pregnancy test at screening and pre-infusion;

7. Throughout this study, the participants will be on stable dosage(s) of medication(s).

Exclusion Criteria

1. Meet criteria for psychotic disorders, e.g. schizophrenia/ schizoaffective disorder.

2. Women who are pregnant or are breast-feeding (because the medical risk of using ketamine during pregnancy and breast-feeding are unknown);

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

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

5. Patients with uncorrected hypothyroidism or hyperthyroidism;

6. Histories of mental retardation

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

8. Drug or alcohol abuse or dependence within the preceding 3 months: phencyclidine (PCP) is especially important in this context because of its resemblance with ketamine not only in structure but also its pharmacodynamic effects on NMDA receptors.

9. Previous recreational use of ketamine;

10. Diagnosis of schizotypal or antisocial personality disorder (since these are known to reduce the possibility of study completion; other Axis II diagnoses will be allowed).

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Cooper Health System

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Basant Pradhan, MD

Role: PRINCIPAL_INVESTIGATOR

Cooper Health System

Locations

Cooper University Hospital

Camden, New Jersey, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Jean Smith, PhD

Role: CONTACT

jean-smith@cooperhealth.edu

856-757-7814

Jean Smith, PhD

Role: CONTACT

Facility Contacts

Basant Pradhan, MD

Role: primary

References

Pradhan B, Kluewer D'Amico J, Makani R, Parikh T. Nonconventional interventions for chronic post-traumatic stress disorder: Ketamine, repetitive trans-cranial magnetic stimulation (rTMS), and alternative approaches. J Trauma Dissociation. 2016;17(1):35-54. doi: 10.1080/15299732.2015.1046101. Epub 2015 Jul 10.

Reference Type: RESULT

PMID: 26162001 (View on PubMed)

Pradhan B, Parikh T, Makani R, Sahoo M. Ketamine, Transcranial Magnetic Stimulation, and Depression Specific Yoga and Mindfulness Based Cognitive Therapy in Management of Treatment Resistant Depression: Review and Some Data on Efficacy. Depress Res Treat. 2015;2015:842817. doi: 10.1155/2015/842817. Epub 2015 Oct 5.

Reference Type: RESULT

PMID: 26509083 (View on PubMed)

Related Links

http://www.ncbi.nlm.nih.gov/pubmed/?term=26509083

Depression Specific Yoga and Mindfulness Based Cognitive Therapy in Management of Treatment Resistant Depression: Review and Some Data on Efficacy.

Other Identifiers

13-078

Identifier Type: -

Identifier Source: org_study_id