PTSDNCT02766192
TIMBER Psychotherapy and Ketamine Single Infusion in Chronic PTSD
A study testing Ketamine and TIMBER Psychotherapy in people with PTSD, run by Cooper Norcross Health at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 to 60 years
- Conditions the study is for
- PTSD
- What is being tested?
- Ketamine and TIMBER Psychotherapy
- Type of treatment
- Injection or infusion, Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2013to Dec 2017
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Men or women, 21-60 years of age;
- Patients attending the outpatient psychiatry clinic of Cooper University Hospital will be screened for this study using DSM-IV diagnostic criteria for PTSD.
- 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;
- 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).
- 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);
- Women of childbearing potential must have a negative pregnancy test at screening and pre-infusion;
- Throughout this study, the participants will be on stable dosage(s) of medication(s).
Who cannot join
- Meet criteria for psychotic disorders, e.g. schizophrenia/ schizoaffective disorder.
- Women who are pregnant or are breast-feeding (because the medical risk of using ketamine during pregnancy and breast-feeding are unknown);
- 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);
- Clinically significant abnormal findings of laboratory parameters, or physical examination;
- Patients with uncorrected hypothyroidism or hyperthyroidism;
- Histories of mental retardation
Show all 10Show fewer
- History of one or more seizures without a clear and resolved etiology;
- 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.
- Previous recreational use of ketamine;
- 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).
Trial locations and contacts
1 site in 1 country.
Jean Smith, PhD contact
United States1 site, 1 recruiting
- Recruiting
Cooper University Hospital
Camden, New Jersey
Basant Pradhan, MD
About this study
Official title: Ketamine and Mindfulness Based Cognitive Therapy (MBCT) in Treatment of Post-Traumatic Stress Disorder (PTSD): Comparison of Treatment Efficacy and Metabolomic Profiles
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
- Being tested
- Ketamine, TIMBER Psychotherapy, Placebo (normal saline)
- Keywords
- ketamine, mindfulness based cognitive therapy, PTSD, trauma memory, memory extinction, memory re-consolidation, metabolomics, TIMBER (Trauma Intervention using Mindfulness Based Extinction and Re-consolidation of trauma memories)
- Medical subject headings
- Stress Disorders, Post-Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KetamineDrug
TIMBER PsychotherapyBehavioural
Placebo (normal saline)Drug
| Study group | Role | What they receive |
|---|---|---|
| TIMBER-Ketamine arm | Experimental | This arm received TIMBER psychotherapy and ketamine infusion. Receives: Drug: Ketamine; Behavioral: TIMBER Psychotherapy |
| TIMBER-placebo arm | Placebo comparator | This arm received TIMBER psychotherapy and placebo (normal saline) infusion. Receives: Behavioral: TIMBER Psychotherapy; Drug: Placebo (normal saline) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline scores on the Clinician Administered PTSD Scale (CAPS) at 25th hours post-infusion
Response (or Relapse status) was assessed by determining the change from baseline scores on the Clinician Administered PTSD Scale (CAPS) at Days-1 (25th hour post-infusion), 7, 14, 21, 28, 35, 42 and 49 and so on following the initiation of the protocol. This was done in this weekly fashion till 3 months after the infusion. A subject was considered to have relapsed when his/her scores were >50 in the CAPS scale and >51 in PTSD Symptom Checklist (PCL) scale respectively. A subject was considered to be a 'Responder' when there was a reduction of 20 or more points of these scores at 25th hours post-infusion compared to his/her baseline scores on CAPS and PCL. To be considered a responder, the response needed to be sustained for 7 days or more.
Measured: For CAPS, change in scores at 25th hour post-infusion compared to the baseline were measured
Change from baseline scores on the PTSD Symptom Checklist (PCL, self-reported) at 25th hours post-infusion
Response (or Relapse status) was assessed by determining the change from baseline scores on the PTSD Symptom Checklist (PCL) at Days-1 (25th hour post-infusion), 7, 14, 21, 28, 35, 42 and 49 and so on following the initiation of the protocol. This was done in this weekly fashion till 3 months after the infusion.
Both CAPS and PCL scales are used in this study to ensure accuracy and objectivity.
Measured: For PCL, change in scores at 25th hour post-infusion compared to the baseline were measured
Secondary outcomes (2)
Change from baseline scores on the Hamilton depression rating scale (17-item version) at 25th hours post-infusion
Measured: For Hamilton depression rating scale, change in scores at 25th hour post-infusion compared to the baseline were measured
Change from baseline scores on the Beck Anxiety Scale at 25th hours post-infusion
Measured: For Beck Anxiety Scale, change in scores at 25th hour post-infusion compared to the baseline were measured
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 May 2016 (estimated)
- Study startAug 2013
- Primary completionDec 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for PTSDStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Cooper Norcross Health
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Basant Pradhan, MD, Principal investigator, Cooper Health System
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02766192
- Sponsor's protocol ID
- 13-078
- Status last verified
- May 2016
- First submitted
- 11 Apr 2016
- Last updated
- 9 May 2016
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Publications
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.
PubMed 26162001Pradhan 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.
PubMed 26509083
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ketamine and Mindfulness Based Cognitive Therapy (MBCT) in Treatment of Post-Traumatic Stress Disorder (PTSD): Comparison of Treatment Efficacy and Metabolomic Profiles
- ClinicalTrials.gov ID
- NCT02766192
- Acronym / sponsor ID
- 13-078
- Conditions
- PTSD
- Keywords
- ketamine, mindfulness based cognitive therapy, PTSD, trauma memory, memory extinction, memory re-consolidation, metabolomics, TIMBER (Trauma Intervention using Mindfulness Based Extinction and Re-consolidation of trauma memories)
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Cooper Norcross HealthUniversity, hospital or other
- Study start
- Aug 2013
- Primary completion
- Dec 2017 (estimated)
- First posted
- 9 May 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| TIMBER-Ketamine arm | Experimental | Drug: Ketamine, Behavioral: TIMBER PsychotherapyThis arm received TIMBER psychotherapy and ketamine infusion. |
| TIMBER-placebo arm | Placebo comparator | Behavioral: TIMBER Psychotherapy, Drug: Placebo (normal saline)This arm received TIMBER psychotherapy and placebo (normal saline) infusion. |
Who may qualify
- Ages
- 21 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Men or women, 21-60 years of age;
- Patients attending the outpatient psychiatry clinic of Cooper University Hospital will be screened for this study using DSM-IV diagnostic criteria for PTSD.
- 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;
- 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).
- 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);
Key exclusion criteria (10 listed)
- Meet criteria for psychotic disorders, e.g. schizophrenia/ schizoaffective disorder.
- Women who are pregnant or are breast-feeding (because the medical risk of using ketamine during pregnancy and breast-feeding are unknown);
- 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);
- Clinically significant abnormal findings of laboratory parameters, or physical examination;
- Patients with uncorrected hypothyroidism or hyperthyroidism;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ketamine | Drug | TIMBER-Ketamine arm |
| TIMBER Psychotherapy | Behavioural | TIMBER-Ketamine arm, TIMBER-placebo arm |
| Placebo (normal saline) | Drug | TIMBER-placebo arm |
Primary outcome
Change from baseline scores on the Clinician Administered PTSD Scale (CAPS) at 25th hours post-infusion
Time frame: For CAPS, change in scores at 25th hour post-infusion compared to the baseline were measured
Response (or Relapse status) was assessed by determining the change from baseline scores on the Clinician Administered PTSD Scale (CAPS) at Days-1 (25th hour post-infusion), 7, 14, 21, 28, 35, 42 and 49 and so on following the initiation of the protocol. This was done in this weekly fashion till 3 months after the infusion. A subject was considered to have relapsed when his/her scores were >50 in the CAPS scale and >51 in PTSD Symptom Checklist (PCL) scale respectively. A subject was considered to be a 'Responder' when there was a reduction of 20 or more points of these scores at 25th hours post-infusion compared to his/her baseline scores on CAPS and PCL. To be considered a responder, the response needed to be sustained for 7 days or more.
Change from baseline scores on the PTSD Symptom Checklist (PCL, self-reported) at 25th hours post-infusion
Time frame: For PCL, change in scores at 25th hour post-infusion compared to the baseline were measured
Response (or Relapse status) was assessed by determining the change from baseline scores on the PTSD Symptom Checklist (PCL) at Days-1 (25th hour post-infusion), 7, 14, 21, 28, 35, 42 and 49 and so on following the initiation of the protocol. This was done in this weekly fashion till 3 months after the infusion. Both CAPS and PCL scales are used in this study to ensure accuracy and objectivity.
2 secondary outcomes
Change from baseline scores on the Hamilton depression rating scale (17-item version) at 25th hours post-infusion
Time frame: For Hamilton depression rating scale, change in scores at 25th hour post-infusion compared to the baseline were measured
Change from baseline scores on the Beck Anxiety Scale at 25th hours post-infusion
Time frame: For Beck Anxiety Scale, change in scores at 25th hour post-infusion compared to the baseline were measured
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 May 2016.
- Results publication: PubMed 26162001Pradhan 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.
- Results publication: PubMed 26509083Pradhan 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.
- Depression Specific Yoga and Mindfulness Based Cognitive Therapy in Management of Treatment Resistant Depression: Review and Some Data on Efficacy.Link provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jean Smith, PhD contact
Basant Pradhan, MD principal investigator
Cooper Health System
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Ketamine and TIMBER Psychotherapy in people with PTSD, run by Cooper Norcross Health at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 9 May 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jean Smith, PhD (856-757-7814, jean-smith@cooperhealth.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline scores on the Clinician Administered PTSD Scale (CAPS) at 25th hours post-infusion (time frame: For CAPS, change in scores at 25th hour post-infusion compared to the baseline were measured). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02766192, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 May 2016.