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Use of Two Deep Brain Stimulation (DBS) Electrodes to Treat Post-Traumatic Tremor

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ClinicalTrials.gov Identifier: NCT00954421
Recruitment Status : Completed
First Posted : August 7, 2009
Results First Posted : June 27, 2014
Last Update Posted : July 25, 2014
Sponsor:
Collaborators:
National Institute of Neurological Disorders and Stroke (NINDS)
Medtronic
Information provided by (Responsible Party):
University of Florida

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Multiple Sclerosis
Intervention Device: Deep Brain Stimulation
Enrollment 16
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Multiple Sclerosis Tremor On VIM and VO
Hide Arm/Group Description

Multiple Sclerosis Tremor On VIM and VO Deep Brain Stimulation

Deep Brain Stimulation: Use of two ipsilateral thalamic Deep Brain Stimulation electrodes (one at the ventralis intermedius nucleus/ventralis oralis posterior nucleus border or VIM and one at the ventralis oralis anterior nucleus/ventralis oralis posterior nucleus border or VO) for treatment of disabling and medication refractory tremor secondary to head trauma or multiple sclerosis.

Period Title: Screening
Started 16
Completed 13
Not Completed 3
Reason Not Completed
screen failures             3
Period Title: Baseline
Started 13
Completed 13
Not Completed 0
Period Title: 6 Months of DBS
Started 13
Completed 12
Not Completed 1
Reason Not Completed
Withdrawal by Subject             1
Period Title: VIM=ON VO=ON at 6 Months
Started 12 [1]
Completed 12
Not Completed 0
[1]
This is the point of evaluation: Order of assessment was random for periods 4-7
Period Title: VIM=OFF VO=OFF at 6 Months
Started 12
Completed 12
Not Completed 0
Period Title: VIM=OFF VO=ON at 6 Months
Started 12
Completed 12
Not Completed 0
Period Title: VIM=ON VO=OFF at 6 Months
Started 12
Completed 11
Not Completed 1
Reason Not Completed
Withdrawal by Subject             1
Arm/Group Title All Subjects
Hide Arm/Group Description All eligible subjects were enrolled and the intent was to treat for six months on dual lead deep brain stimulation in the VIM and VO regions.
Overall Number of Baseline Participants 13
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 13 participants
41.54  (15.03)
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants
<=18 years
0
   0.0%
Between 18 and 65 years
12
  92.3%
>=65 years
1
   7.7%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants
Female
11
  84.6%
Male
2
  15.4%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 13 participants
13
Baseline Total Fain-Tolosa-Marin Tremor Rating Scale (TRS)   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 13 participants
56.2  (9.4)
[1]
Measure Description: Tremor was evaluated using the Fain-Tolosa-Marin Tremor Rating Scale (TRS). Score was obtained by summing all 21 items, each of which assessed tremor on a scale of 0-4. Because some of the 21 items contained more than one subsection, total maximum score was 144, and minimum score was 0. Higher scores represent worse tremor.
1.Primary Outcome
Title Fain-Tolosa-Marin Tremor Rating Scale (TRS) Change Score for Both VIM and VO ON (Baseline Minus 6 Months Post-implant)
Hide Description

Tremor was evaluated using the Fain-Tolosa-Marin Tremor Rating Scale (TRS). Score was obtained by summing all 21 items, each of which assessed tremor on a scale of 0-4. Because some of the 21 items contained more than one subsection, total maximum score was 144, and minimum score was 0. Higher scores represent worse tremor.

Both VIM and VO stimulators will be turned ON and TRS score at 6 months will be compared to pre-implant (baseline).

Time Frame Change from Baseline to Six Months
Hide Outcome Measure Data
Hide Analysis Population Description
All Subjects completing Period 4
Arm/Group Title Multiple Sclerosis Tremor On VIM and VO
Hide Arm/Group Description:

Multiple Sclerosis Tremor On VIM and VO Deep Brain Stimulation

Deep Brain Stimulation: Use of two ipsilateral thalamic Deep Brain Stimulation electrodes (one at the ventralis intermedius nucleus/ventralis oralis posterior nucleus border or VIM and one at the ventralis oralis anterior nucleus/ventralis oralis posterior nucleus border or VO) for treatment of disabling and medication refractory tremor secondary to head trauma or multiple sclerosis.

Overall Number of Participants Analyzed 12
Mean (Standard Deviation)
Unit of Measure: units on a scale
-17.6  (19.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Multiple Sclerosis Tremor On VIM and VO
Comments The null hypothesis is that the mean change in Tremor Rating Scale score from baseline to six months post-implant (with VIM and VO stimulators turned ON) will be zero
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .026
Comments [Not Specified]
Method two-sided sign-rank test
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -17.6
Confidence Interval (2-Sided) 95%
-30.61 to -4.65
Parameter Dispersion
Type: Standard Deviation
Value: 19.4
Estimation Comments p-value assessed via sign-rank test (pre-planned method)
2.Secondary Outcome
Title Fain-Tolosa-Marin Tremor Rating Scale (TRS) Change Score for Either VIM or VO On, and for Both VIM and VO Off (Baseline Minus 6 Months Post-implant)
Hide Description

Tremor was evaluated using the Fain-Tolosa-Marin Tremor Rating Scale (TRS). Score was obtained by summing all 21 items, each of which assessed tremor on a scale of 0-4. Because some of the 21 items contained more than one subsection, total maximum score was 144, and minimum score was 0. Higher scores represent worse tremor.

Both VIM and VO stimulators will be turned ON and TRS score at 6 months will be compared to pre-implant (baseline).

Either VO or VIM stimulator will be turned on (as opposed to both stimulators, as in outcome measure 1), and change in Tremor Rating Scale scores will be compared. The effects of each individual stimulator will also be compared to both being turned on.

Time Frame Baseline to Six Months
Hide Outcome Measure Data
Hide Analysis Population Description
Patients completing 6 months were tested for VIM and VO both on vs. both off. Score is TRS scale with both off minus both on. Positive value favors DBS.
Arm/Group Title TRS Scale Both Off vs Both on at 6 Months TRS Scale Vo Only on vs. Vim Only on at 6 Months
Hide Arm/Group Description:

Multiple Sclerosis Tremor On VIM and VO Deep Brain Stimulation Periods 4 vs. 5(Both OFF- Both On) at 6 months.

Deep Brain Stimulation: Use of two ipsilateral thalamic Deep Brain Stimulation electrodes (one at the ventralis intermedius nucleus/ventralis oralis posterior nucleus border or VIM and one at the ventralis oralis anterior nucleus/ventralis oralis posterior nucleus border or VO) for treatment of disabling and medication refractory tremor secondary to head trauma or multiple sclerosis.

Multiple Sclerosis Tremor On VIM and VO Deep Brain Stimulation Periods 4 vs. 5(Vo only on -VM only on at 6 months.

Deep Brain Stimulation: Use of two ipsilateral thalamic Deep Brain Stimulation electrodes (one at the ventralis intermedius nucleus/ventralis oralis posterior nucleus border or VIM and one at the ventralis oralis anterior nucleus/ventralis oralis posterior nucleus border or VO) for treatment of disabling and medication refractory tremor secondary to head trauma or multiple sclerosis.

Overall Number of Participants Analyzed 12 11
Mean (Standard Deviation)
Unit of Measure: units on a scale
8.4  (9.1) 0.73  (8.49)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TRS Scale Both Off vs Both on at 6 Months
Comments The null hypothesis is that difference in change in Tremor Rating Scale (TRS) score from baseline to 6 months when both stimulators are on (VIM and VO), versus when both stimulators are off, will be zero (i.e., that there will be no difference in effect between having both stimulators on versus both stimulators off)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.011
Comments Sign rank test was pre-planned for P-value
Method Sign-Rank test
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 8.4
Confidence Interval (2-Sided) 95%
2.2 to 14.5
Parameter Dispersion
Type: Standard Deviation
Value: 9.1
Estimation Comments p-value assessed using sign rank test
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection TRS Scale Vo Only on vs. Vim Only on at 6 Months
Comments The null hypothesis is that difference in change in Tremor Rating Scale (TRS) score from baseline to 6 months when VO is on and VIM is off, versus when VIM is on and VO is off, will be zero (i.e., that there will be no difference in effect between having exclusively VIM versus VO on)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .68
Comments [Not Specified]
Method two-sided sign rank test
Comments two sided sign rank test as pre-planned
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value .73
Confidence Interval 95%
-4.96 to 6.42
Parameter Dispersion
Type: Standard Deviation
Value: 8.49
Estimation Comments [Not Specified]
Time Frame Baseline, 6 months, 24 months
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Multiple Sclerosis Tremor On VIM and VO
Hide Arm/Group Description

Multiple Sclerosis Tremor On VIM and VO Deep Brain Stimulation

Deep Brain Stimulation: Use of two ipsilateral thalamic Deep Brain Stimulation electrodes (one at the ventralis intermedius nucleus/ventralis oralis posterior nucleus border or VIM and one at the ventralis oralis anterior nucleus/ventralis oralis posterior nucleus border or VO) for treatment of disabling and medication refractory tremor secondary to head trauma or multiple sclerosis.

All-Cause Mortality
Multiple Sclerosis Tremor On VIM and VO
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Multiple Sclerosis Tremor On VIM and VO
Affected / at Risk (%) # Events
Total   6/13 (46.15%)    
Infections and infestations   
Superficial Wound Infection *  1/13 (7.69%)  1
Infection at site of IPG (pulse generator for DBS implant) *  1/13 (7.69%)  1
Injury, poisoning and procedural complications   
Death * [1]  1/13 (7.69%)  1
Right fractured femur *  1/13 (7.69%)  1
Nervous system disorders   
Exacerbation of Multple Sclerosis symptoms * [2]  1/13 (7.69%)  3
Psychiatric disorders   
Change in mental status *  2/13 (15.38%)  2
Surgical and medical procedures   
Complications with device hardware * [3]  2/13 (15.38%)  2
Implantation of tunneled intrathecal catheter and subcutaneous implantation of a programmable pump *  1/13 (7.69%)  1
*
Indicates events were collected by non-systematic assessment
[1]
drowning due to accident (related to her multiple sclerosis)
[2]
affecting facial never numbness (1 case), progressive weakening (2 cases)
[3]
fractured DBS cables (1 case), erosion over hardware (1 case)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Multiple Sclerosis Tremor On VIM and VO
Affected / at Risk (%) # Events
Total   13/13 (100.00%)    
Eye disorders   
eyelid fluttering *  1/13 (7.69%)  2
Gastrointestinal disorders   
Gastrointestinal discomfort * [1]  3/13 (23.08%)  6
General disorders   
speech difficulty * [2]  4/13 (30.77%)  6
swallowing difficulty *  1/13 (7.69%)  1
lightheadedness *  1/13 (7.69%)  2
worsened balance *  1/13 (7.69%)  1
headache *  6/13 (46.15%)  8
pain behind left ear *  1/13 (7.69%)  1
pain under left eye *  1/13 (7.69%)  1
neck pain *  1/13 (7.69%)  1
back pain *  1/13 (7.69%)  1
lower breast pain *  1/13 (7.69%)  1
internal capsule pulling *  1/13 (7.69%)  1
pain on left side of head *  1/13 (7.69%)  1
eczema *  1/13 (7.69%)  1
Immune system disorders   
worsening of nasal allergies *  1/13 (7.69%)  1
Infections and infestations   
Clostridium Difficile Infection *  1/13 (7.69%)  1
Fever *  1/13 (7.69%)  1
urinary tract infection *  2/13 (15.38%)  3
Injury, poisoning and procedural complications   
fall *  3/13 (23.08%)  5
scalp tenderness *  1/13 (7.69%)  1
head pain at crania cap *  1/13 (7.69%)  1
pinching at site of pulse generator *  2/13 (15.38%)  2
scar tissue formation at site of DBS *  1/13 (7.69%)  1
irritation at site of pulse generator *  3/13 (23.08%)  3
Musculoskeletal and connective tissue disorders   
weakness *  3/13 (23.08%)  5
decreased mobility *  2/13 (15.38%)  5
Nervous system disorders   
facial numbness *  1/13 (7.69%)  1
trigeminal neuralgia *  1/13 (7.69%)  1
Twiddler syndrome *  2/13 (15.38%)  2
intra-operative seizure *  1/13 (7.69%)  1
tremor in bottom lip *  1/13 (7.69%)  1
nocturnal myoclonus of lower extremities *  1/13 (7.69%)  1
Psychiatric disorders   
crying *  3/13 (23.08%)  3
irritability *  1/13 (7.69%)  1
fatigue *  4/13 (30.77%)  5
tremor in abdomen *  1/13 (7.69%)  1
insomnia *  2/13 (15.38%)  2
Respiratory, thoracic and mediastinal disorders   
laryngitis *  1/13 (7.69%)  1
*
Indicates events were collected by non-systematic assessment
[1]
diarrhea (1 case), nausea (1 case), vomiting (1 case), constipation (2 cases)
[2]
slurred speech (3 cases), slower speech (2 cases), stuttering speech (1 case)
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Kelly Foote
Organization: University of Florida
Phone: 352-273-5550
EMail: foote@neurosurgery.ufl.edu
Layout table for additonal information
Responsible Party: University of Florida
ClinicalTrials.gov Identifier: NCT00954421     History of Changes
Other Study ID Numbers: 461-2006
K23NS052557 ( U.S. NIH Grant/Contract )
First Submitted: July 27, 2009
First Posted: August 7, 2009
Results First Submitted: April 15, 2014
Results First Posted: June 27, 2014
Last Update Posted: July 25, 2014