Transcranial Magnetic Stimulation (TMS) to Treat mTBI and PTSD

NCT ID: NCT02458521

Last Updated: 2015-11-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-08-31

Study Completion Date

2019-05-31

Brief Summary

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The overall objective of this project is to determine the efficacy and tolerability of TMS for mild Traumatic Brain Injury (mTBI) with PTSD symptoms and correlate treatment response with anatomical and biological factors unique to each service member (SM). Exploratory work will be done to look at the neuronal and biological changes that may occur over the course of TMS treatment.

Detailed Description

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The primary objectives of this study are:

1. To assess the change on the Rivermead Post-Concussion Symptoms Questionnaire (RPQ) and the PTSD Check List-Civilian Version (PCL-C) administered pre-treatment, then bi-weekly (weeks 2, 4, 6) during a 7 week treatment course, then monthly for 3 months following treatment.

Hypothesis: The addition of high frequency left pre-frontal and low frequency right pre-frontal cortical stimulation will improve symptom reporting on the RPQ and PCL-C in service members with mTBI and PTSD symptoms as compared to sham treatment.
2. To assess the tolerability of TMS in subjects as measured by side effects in active TMS compared with sham treatment.

Hypothesis: TMS will prove safe and tolerable in service members with mTBI and PTSD.

The secondary objectives of this study are:

1. To assess whether TMS results in an improvement in mood as measured by the Quick Inventory of Depressive Symptomatology - Self Report (QIDS-SR), general life functioning (physical, cognitive, emotional, behavioral, and social problems) as measured by the Mayo-Portland Adaptability Inventory - military (MPAI-m), life satisfaction as measured by the Satisfaction With Life Scale (SWLS), and suicidality as measured by the Beck Scale for Suicidal Ideation (BSS).

Hypothesis: TMS will result in an improvement in mood, general life functioning, and life satisfaction, as well as a reduction in suicidality.
2. To assess the durability of any improvement realized by TMS over the course of three months following the conclusion of sessions.

Hypothesis: The improvement realized by 7 weeks of TMS will prove stable, showing effects up to 3 months after the conclusion of active treatment.
3. To assess structural neuronal changes over the course of active vs. sham TMS as measured by MRI.

Hypothesis 1: Analysis of structural MRI (3D T1-weighted) will reveal increased volume of the hippocampus and anterior cingulate cortex in service members who improve in PTSD symptoms (as measured by the PCL-C).

Hypothesis 2: Microstructural MRI (DTI) will reveal FA increase in the corpus callosum and the uncinated fasciculus in service members who improve in measures of mTBI (i.e., Rivermead Post Concussion Symptoms Questionnaire).
4. To assess metabolic neuronal changes that occur over the course of active vs. sham TMS as measured by PET.

Hypothesis 1: TMS will result in increased glucose uptake in the ipsilateral and contralateral cerebral hemispheres for those who show significant improvements in the symptomatic measures of TBI (i.e. RPQ and MPAI-m).

Hypothesis 2: TMS will result in decreased glucose uptake in the dorsal anterior cingulate/mid cingulate cortex (dACC/MCC) and in the bilateral amygdala for those service members with significant improvements in the symptomatic measures of PTSD and mood (i.e. PTSD Checklist and QIDS-SR).
5. To examine the mechanism of action of TMS through looking at the metabolic changes that occur during a TMS session.

Hypothesis: There will be increased glucose uptake in the left prefrontal cortex and decreased glucose uptake in the right prefrontal cortex immediately after active TMS as compared to sham.
6. Exploratory: To assess biological changes that result from TMS therapy and to determine how biomarkers relate to changes in PTSD symptoms.
7. Exploratory: To examine how single gene polymorphisms (SNPs) in serotonin genes may relate to TMS response and symptom change.

Conditions

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Traumatic Brain Injury Post-Traumatic Stress Disorder

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Transcranial Magnetic Stimulation

TMS sessions will consist of both 10Hz left pre-frontal stimulation for 3,500 pulses followed by 1Hz right pre-frontal stimulation for 1,500 pulses per session, for a total stimulation time of approximately one hour per session.

Group Type EXPERIMENTAL

Transcranial Magnetic Stimulation

Intervention Type DEVICE

Treatment will consist of 30 sessions of TMS over approximately 7 weeks. More specifically, the active or sham TMS treatments will be conducted five times a week for 5 consecutive weeks, followed by a tapering of three sessions during week 6 and two sessions during week 7. TMS sessions will consist of both 10 Hz left pre-frontal stimulation for 3,500 pulses followed by 1 Hz right pre-frontal stimulation for 1,500 pulses per session, for a total stimulation time of approximately one hour per session. These pulse sequences have theoretical targets that may be implicated in conditions of poor resiliency, apathy, depression and anxiety.

Sham Transcranial Magnetic Stimulation

Sham TMS treatments will be conducted five times a week for 5 consecutive weeks, followed by a tapering of three sessions during week 6 and two sessions during week 7.

Group Type SHAM_COMPARATOR

Sham Transcranial Magnetic Stimulation

Intervention Type DEVICE

Treatment will consist of 30 sessions of TMS over approximately 7 weeks. More specifically, the active or sham TMS treatments will be conducted five times a week for 5 consecutive weeks, followed by a tapering of three sessions during week 6 and two sessions during week 7. The TMS system will have three coils, one designated active and the other two unlabeled and identical in appearance, weight, and noises emitted, one of which will be active and one of which will be sham.

Interventions

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Transcranial Magnetic Stimulation

Treatment will consist of 30 sessions of TMS over approximately 7 weeks. More specifically, the active or sham TMS treatments will be conducted five times a week for 5 consecutive weeks, followed by a tapering of three sessions during week 6 and two sessions during week 7. TMS sessions will consist of both 10 Hz left pre-frontal stimulation for 3,500 pulses followed by 1 Hz right pre-frontal stimulation for 1,500 pulses per session, for a total stimulation time of approximately one hour per session. These pulse sequences have theoretical targets that may be implicated in conditions of poor resiliency, apathy, depression and anxiety.

Intervention Type DEVICE

Sham Transcranial Magnetic Stimulation

Treatment will consist of 30 sessions of TMS over approximately 7 weeks. More specifically, the active or sham TMS treatments will be conducted five times a week for 5 consecutive weeks, followed by a tapering of three sessions during week 6 and two sessions during week 7. The TMS system will have three coils, one designated active and the other two unlabeled and identical in appearance, weight, and noises emitted, one of which will be active and one of which will be sham.

Intervention Type DEVICE

Eligibility Criteria

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Inclusion Criteria

1. Military health care beneficiary for enrollment (loss of benefits will not require separation from the study).
2. Over the age of 18 years.
3. Presence of mTBI (based on standard Veterans Affairs (VA)/ Department of Defense (DoD) criteria).
4. Presence of PTSD symptoms (PCL score over 30).

Exclusion Criteria

1. Evidence of moderate or severe TBI (based on standard VA/DoD criteria). Incidental neuroimaging findings that may or may not be related to trauma (e.g. white matter hyperintensities on structural MRI) are not sufficient to identify a subject as a moderate TBI if other severity markers fall in the mild TBI range.
2. History of seizure, bipolar disorder, schizophrenia, or current dependence to psychoactive substance(s).
3. History of severe or recent heart disease.
4. Vascular, traumatic, tumoral, infectious, or metabolic lesion of the brain.
5. Use of medications that potentially lower seizure threshold without concomitant administration of anticonvulsant drugs which may protect against seizure occurrence.
6. Not a suitable candidate for the study as determined by the PI.
7. Pregnancy or plans to become pregnant during the course of the study (determined via urine-pregnancy test).
8. Presence of metallic hardware in close contact to the discharging coil (e.g. cochlear implants, internal pulse generator).
9. Presence of implanted brain electrodes (cortical or deep-brain electrodes).
10. MRI portion: Presence of metal fragments or devices (cardiac pacemaker, neural stimulator, etc.), which are determined by a radiologist to contraindicate MRI (at 3 Tesla). Also, presence of metal (such as dental braces) which causes significant degradation of the MRI signal.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Center for Neuroscience and Regenerative Medicine (CNRM)

FED

Sponsor Role collaborator

Walter Reed National Military Medical Center

FED

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Geoffrey G Grammer, M.C.

Role: STUDY_CHAIR

National Intrepid Center of Excellence

Paul F Pasquina, M.D.

Role: PRINCIPAL_INVESTIGATOR

Walter Reed National Military Medical Center

Louis M French, Psy.D

Role: STUDY_CHAIR

Walter Reed National Military Medical Center

Nancy de Almeida, RN

Role: STUDY_CHAIR

Walter Reed National Military Medical Center

Locations

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National Intrepid Center of Excellence, Walter Reed National Military Medical Center

Bethesda, Maryland, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Paul Pasquina, M.D.

Role: CONTACT

301-310-2460

Ariana C Gover-Chamlou, B.A.

Role: CONTACT

3013198148

Facility Contacts

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Ariana C Gover-Chamlou, BA

Role: primary

301-319-8148

Nancy de Almeida, RN

Role: backup

3014001234

Other Identifiers

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CNRM 0048

Identifier Type: OTHER

Identifier Source: secondary_id

Protocol # [397662]

Identifier Type: -

Identifier Source: org_study_id