Clinical trial NCT02458521: Transcranial Magnetic Stimulation (TMS) to Treat mTBI and PTSD
Official title: A Study of Bilateral Prefrontal Transcranial Magnetic Stimulation (TMS) to Treat the Symptoms of Mild TBI (mTBI) and PTSD
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Traumatic Brain Injury
Post-Traumatic Stress Disorder
Lead sponsor: Walter Reed National Military Medical Center
Sponsor class: FED
Collaborators: name: Center for Neuroscience and Regenerative Medicine (CNRM)
First posted: 2015-06-01
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Rivermead Post-Concussion Symptoms Questionnaire (RPQ)
timeFrame: Measured to compare changes from Baseline; during weeks 2, 4, and 6 of treatment; and during the Month 1, Month 2, and Month 3 follow up visits after treatment ends.
measure: PTSD Check List-Civilian (PCL-C)
timeFrame: Measured to compare changes from Baseline; during weeks 2, 4, and 6 of treatment; and during the Month 1, Month 2, and Month 3 follow up visits after treatment ends.
Secondary outcomes:
measure: Quick Inventory of Depressive Symptomatology, Self-Report (QIDS-SR)
timeFrame: Measured to compare changes from Baseline; during weeks 2, 4, 6 of treatment; and during the Month 1, Month 2, and Month 3 follow up visits after treatment ends.
measure: Beck Scale for Suicide Ideation (BSS)
timeFrame: Measured to compare changes from Baseline; during weeks 2, 4, 6 of treatment; and during the Month 1, Month 2, and Month 3 follow up visits after treatment ends.
measure: Mayo-Portland Adaptability Inventory-Military Edition (MPAI-m)
timeFrame: Measured to compare changes from Baseline; during weeks 2, 4, 6 of treatment; and during the Month 1, Month 2, and Month 3 follow up visits after treatment ends.
measure: Satisfaction with Life Scale (SWLS)
timeFrame: Measured to compare changes from Baseline; during weeks 2, 4, 6 of treatment; and during the Month 1, Month 2, and Month 3 follow up visits after treatment ends.
Other outcomes:
measure: Pain Rating
timeFrame: Measured to compare changes from Baseline; during weeks 2, 4, 6 of treatment; and during the Month 1, Month 2, and Month 3 follow up visits after treatment ends.
measure: Automated Neuropsychological Assessment Metrics (ANAM)
timeFrame: Will be administered 3 times to compare changes from (1) Baseline (within 30 days of initiating TMS or Sham treatment); (2) prior to a session during week 2 of TMS or Sham treatment; and (3) at the completion of TMS or Sham treatment (week 7).
measure: Structural Neuronal Changes to be assessed by MRI Assessment
timeFrame: Measured at Baseline and compared to results at completion of treatment (week 7).
measure: Metabolic Neuronal Changes to be assessed by PET Assessment (FDG-PET)
timeFrame: Measured at Baseline and compared to results from week 2 of treatment, and at completion of treatment (week 7).
measure: Biomarker Assessment: Blood Samples
timeFrame: Measured at Baseline and compared to changes at week 7 of treatment, and the Month 3 follow-up visit post-treatment.
measure: Biomarker Assessment: Saliva Samples
timeFrame: Measured at Baseline and compared to changes at week 7 of treatment, and the Month 3 follow-up visit post-treatment.
Locations:
city: Bethesda
country: United States
facility: National Intrepid Center of Excellence, Walter Reed National Military Medical Center
state: Maryland
Study officials:
affiliation: National Intrepid Center of Excellence
name: Geoffrey G Grammer, M.C.
role: STUDY_CHAIR
affiliation: Walter Reed National Military Medical Center
name: Paul F Pasquina, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Walter Reed National Military Medical Center
name: Louis M French, Psy.D
role: STUDY_CHAIR
affiliation: Walter Reed National Military Medical Center
name: Nancy de Almeida, RN
role: STUDY_CHAIR
References: