Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
The purpose of this study is to examine the safety and efficacy of repetitive transcranial magnetic stimulation (rTMS) combined with Amantadine relative to rTMS Alone and Amantadine Alone for persons in chronic states of seriously impaired consciousness. The hypothesis is that provision of rTMS+Amantadine will provide a safe yet synergistic effect that induces or accelerates functional recovery.
The R21 research objective is to examine the safety and efficacy of repetitive transcranial magnetic stimulation (rTMS) combined with Amantadine (TMS + Amantadine) relative to rTMS Alone and Amantadine Alone for persons in chronic states of seriously impaired consciousness. The hypothesis is that provision of rTMS+Amantadine will provide a safe yet synergistic effect that induces or accelerates functional recovery. This hypothesis is based on (a) preliminary data indicating partially improved neurobehavioral functioning mechanistically related to rTMS-induced neural activity and connectivity as well as improved integrity of white fiber tracts, (b) relationship between dopamine (DA) and common traumatic brain injury (TBI) impairments, (c) role of DA in mediating consciousness, (d) the commonality between and DA and rTMS-targeted pathways, (e) clinical efficacy and safety of Amantadine, (f) mechanisms of action of Amantadine, and (g) the association between rTMS and Amantadine with up-regulating brain derived neurotrophic factor. The rationale is that pairing rTMS with Amantadine will have a complementary and synergistic effect on factors promoting conscious behavior. The specific aims are to: (1) Demonstrate that rTMS+Amantadine is safely tolerated, (2) Determine neurobehavioral effect of rTMS+Amantadine, and (3) Characterize pre-and post-treatment neural changes in neural activation. Aim 1 is based on our preliminary safety data and safety data regarding Amantadine. To address Aims 2 & 3 we use a repeated measures baseline control design with randomized treatment orders yielding three treatment groups; rTMS + Amantadine, rTMS Alone and Amantadine Alone. Analyses for Aims 2 and 3 involve comparing these treatment groups according to neurobehavioral growth trajectories, mean amount of neural activation and connectivity within and between brain regions, and indices of fiber tract directionality.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| rTMS Alone followed by rTMS+AMA | Experimental | Subjects assigned to rTMS Alone will receive 30 sessions of rTMS. Two rTMS sessions will be provided per day, four days per week.After first completing rTMS Alone, subjects will receive rTMS plus Amantadine. A total of 30 rTMS sessions are provided, 2 rTMS sessions per day, four days per week, while receiving 200mg of Amantadine daily. |
|
| AMA Alone followed by rTMS+AMA | Experimental | Subjects who are assigned to the Amantadine Alone group will receive 28 doses of Amantadine (100mg BID) every day for 28 days. After first completing Amantadine Alone subjects will receive rTMS plus Amantadine. A total of 30 rTMS sessions are provided, 2 rTMS sessions per day, four days per week, while receiving 200mg of Amantadine daily. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| rTMS | Device |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Intensity of Adverse Event | If an adverse event occurred, the intensity was also indicated. The intensity of an adverse event was determined using a scale from 1-5 with 5 being the worst. The purpose of the study is to examine safety of rTMS combined with AMA relative to rTMS Alone and AMA alone. Results are not reported "per arm" rather, the arms are combined so as to compare the outcome when the interventions are provided separately (i.e., rTMS alone and amantadine alone) vs interventions are combined (rTMS +Amantadine alone). | 30 days after treatment "alone" and an additional 30 days after treatment "combined" (i.e., 60 days) |
Not provided
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Theresa BenderPape, DrPH | Edward Hines Jr. VA Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Northwestern Memorial Hospital | Chicago | Illinois | 60611 | United States | ||
| Edward Hines, Jr. VA Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 16983227 | Background | Pape TL, Rosenow J, Lewis G. Transcranial magnetic stimulation: a possible treatment for TBI. J Head Trauma Rehabil. 2006 Sep-Oct;21(5):437-51. doi: 10.1097/00001199-200609000-00063. | |
| 20633400 | Background | Louise-Bender Pape T, Rosenow J, Lewis G, Ahmed G, Walker M, Guernon A, Roth H, Patil V. Repetitive transcranial magnetic stimulation-associated neurobehavioral gains during coma recovery. Brain Stimul. 2009 Jan;2(1):22-35. doi: 10.1016/j.brs.2008.09.004. Epub 2008 Oct 23. |
Not provided
Not provided
nothing to report
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | rTMS Alone Followed by rTMS+AMA | Subjects assigned to rTMS Alone will receive 30 sessions of rTMS. Two rTMS sessions will be provided per day, four days per week.upon completion of assigned treatment order, the subject will then receive 30 sessions of combination therapy of rTMS + Amantadine rTMS |
| FG001 | AMA Alone Followed by rTMS+AMA | Subjects who are assigned to the Amantadine Alone group will receive 28 doses of Amantadine (100mg BID) every day for 28 days. upon completion of assigned treatment order, the subject will then receive 30 sessions of combination therapy of rTMS + Amantadine Amantadine |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | rTMS First | Subjects assigned to rTMS Alone will receive 30 sessions of rTMS. Two rTMS sessions will be provided per day, four days per week. rTMS |
| BG001 | Amantadine First | Subjects who are assigned to the Amantadine Alone group will receive 28 doses of Amantadine (100mg BID) every day for 28 days. Amantadine |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Intensity of Adverse Event | If an adverse event occurred, the intensity was also indicated. The intensity of an adverse event was determined using a scale from 1-5 with 5 being the worst. The purpose of the study is to examine safety of rTMS combined with AMA relative to rTMS Alone and AMA alone. Results are not reported "per arm" rather, the arms are combined so as to compare the outcome when the interventions are provided separately (i.e., rTMS alone and amantadine alone) vs interventions are combined (rTMS +Amantadine alone). | Results are reported both "per arm" at the end of 30 days when a single treatment (either rTMS or AMA) was ended, and additional results are reported with both arms combined to report the outcome after 60 days | Posted | Mean | Standard Deviation | score on a scale | 30 days after treatment "alone" and an additional 30 days after treatment "combined" (i.e., 60 days) |
|
3 months and 6 months
A Clinical Data Monitoring Log was used to record. Most were collected daily. CNS changes were collected once during MRI scan. clinical indices include fatigue, fever, hypertension, hypotension, infection at IV site, weight loss/gain, seizures, skin breakdown at IV site, skin breakdown on scalp, general skin breakdown, sweating and neurochecks hourly between rTMS sessions on the same day.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | rTMS Alone | Subjects assigned to rTMS Alone 30 sessions of rTMS. Two rTMS sessions will be provided per day, four days per week. |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Fatigue | General disorders | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Theresa Bender-Pape | Edward Hines VA Hospital | 708-202-4953 | Theresa.BenderPape@va.gov |
Not provided
| ID | Term |
|---|---|
| D000070642 | Brain Injuries, Traumatic |
| D018458 | Persistent Vegetative State |
| ID | Term |
|---|---|
| D001930 | Brain Injuries |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D050781 | Transcranial Magnetic Stimulation |
| D000547 | Amantadine |
| ID | Term |
|---|---|
| D055909 | Magnetic Field Therapy |
| D013812 | Therapeutics |
| D000218 | Adamantane |
| D001952 | Bridged-Ring Compounds |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Amantadine | Drug |
|
|
| Hines |
| Illinois |
| 60141 |
| United States |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Full Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
Subjects assigned to start with rTMS Alone
| OG001 | rTMS+AMA | All subjects that received rTMS plus Amantadine. A total of 30 rTMS sessions are provided, 2 rTMS sessions per day, four days per week, while receiving 200mg of Amantadine daily. |
| OG002 | AMA Alone | Subjects assigned to start with amantadine alone |
|
|
|
| 0 |
| 2 |
| 0 |
| 2 |
| 2 |
| 2 |
| EG001 | rTMS+AMA | Subjects who are assigned to the Amantadine Alone group will receive 28 doses of Amantadine (100mg BID) every day for 28 days.Then, A total of 30 rTMS sessions are provided, 2 rTMS sessions per day, four days per week, while receiving 200mg of Amantadine daily. | 0 | 4 | 0 | 4 | 4 | 4 |
| EG002 | AMA Alone | Subjects who are assigned to the Amantadine Alone group will receive 28 doses of Amantadine (100mg BID) every day for 28 days. | 0 | 2 | 0 | 2 | 2 | 2 |
| Fever | General disorders | Systematic Assessment |
|
| hypertension | General disorders | Systematic Assessment |
|
| Hypotension | General disorders | Systematic Assessment |
|
| Infection at IV site | General disorders | Systematic Assessment |
|
| Weight Loss | General disorders | Systematic Assessment |
|
| Neurocheck | General disorders | Systematic Assessment |
|
| Seizure | General disorders | Systematic Assessment |
|
| Skin breakdown at venous site | General disorders | Systematic Assessment |
|
| General Skin Integrity | General disorders | Systematic Assessment |
|
| Skin breakdown at scalp | General disorders | Systematic Assessment |
|
| Sweating | General disorders | Systematic Assessment |
|
Not provided
Not provided
| D006259 |
| Craniocerebral Trauma |
| D020196 | Trauma, Nervous System |
| D014947 | Wounds and Injuries |
| D001925 | Brain Damage, Chronic |
| D014474 | Unconsciousness |
| D003244 | Consciousness Disorders |
| D019954 | Neurobehavioral Manifestations |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D006844 |
| Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |