COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Cognitive Dysfunction in Parkinson's Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02346708
Recruitment Status : Active, not recruiting
First Posted : January 27, 2015
Results First Posted : December 9, 2020
Last Update Posted : December 9, 2020
Sponsor:
Collaborators:
National Institutes of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
University of Colorado, Denver

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Outcomes Assessor);   Primary Purpose: Treatment
Condition Parkinson's Disease
Interventions Device: Real TMS
Device: Sham TMS
Enrollment 49
Recruitment Details Recruitment was conducted in the United States at one site: University of Colorado Denver - Anschutz Medical Campus. The first participant was enrolled in May 19, 2014.
Pre-assignment Details 70 participants were assessed for eligibility (following Inclusion and exclusion criteria), 21 were screen failures, 49 participants were randomized to treatment.
Arm/Group Title Real TMS Sham TMS
Hide Arm/Group Description

TMS will be administered using a 70-mm diameter air-cooled figure-of-8 coil and SuperRapid2 Magstim Stimulator. Repetitive pulses will be delivered to the right and left dorsolateral pre-frontal cortex (Brodmann area 46) using a frameless stereotactic navigation system and the subject's magnetic resonance imaging (MRI) in Brainsight software. Stimuli will be delivered at 20 Hz at 90% resting motor threshold (rMT) for 25 trains of 30 pulses per train, inter-train interval of 30 seconds for a total of 750 pulses per hemisphere. This dose and duration of repetitive TMS (rTMS) is based on physiological studies of healthy adults and treatment studies of cognition in PD and Alzheimer's disease. Side of first stimulation (left vs right hemisphere) will be counterbalanced across subjects.

Real TMS: real treatment

Sham stimulation will be delivered using a sham coil fitted with electrodes to mimic both the auditory and somatic sensation of real TMS.

Sham TMS: placebo treatment

Period Title: Overall Study
Started 24 25
Completed 22 24
Not Completed 2 1
Reason Not Completed
Adverse Event             2             0
Protocol Violation             0             1
Arm/Group Title Real TMS Sham TMS Total
Hide Arm/Group Description

TMS will be administered using a 70-mm diameter air-cooled figure-of-8 coil and SuperRapid2 Magstim Stimulator. Repetitive pulses will be delivered to the right and left dorsolateral pre-frontal cortex (Brodmann area 46) using a frameless stereotactic navigation system and the subject's magnetic resonance imaging (MRI) in Brainsight software. Stimuli will be delivered at 20 Hz at 90% resting motor threshold (rMT) for 25 trains of 30 pulses per train, inter-train interval of 30 seconds for a total of 750 pulses per hemisphere. Stimulation will be delivered for 10 consecutive days, excluding the weekends. This dose and duration of repetitive TMS (rTMS) is based on physiological studies of healthy adults and treatment studies of cognition in PD and Alzheimer's disease. Side of first stimulation (left vs right hemisphere) will be counterbalanced across subjects.

Real TMS: real treatment

Sham stimulation will be delivered using a sham coil fitted with electrodes to mimic both the auditory and somatic sensation of real TMS.

Sham TMS: placebo treatment

Total of all reporting groups
Overall Number of Baseline Participants 22 24 46
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants 24 participants 46 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
8
  36.4%
7
  29.2%
15
  32.6%
>=65 years
14
  63.6%
17
  70.8%
31
  67.4%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 22 participants 24 participants 46 participants
67.4  (7.2) 69.5  (8) 68.5  (7.6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants 24 participants 46 participants
Female
6
  27.3%
7
  29.2%
13
  28.3%
Male
16
  72.7%
17
  70.8%
33
  71.7%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants 24 participants 46 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
1
   4.5%
0
   0.0%
1
   2.2%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
1
   4.5%
0
   0.0%
1
   2.2%
White
20
  90.9%
24
 100.0%
44
  95.7%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 22 participants 24 participants 46 participants
22 24 46
1.Primary Outcome
Title Change in Magnetoencephalography (MEG) Connectivity Measures
Hide Description Our MEG outcome will be a change in small-worldness, global efficiency, nodal efficiency and degree distribution pre-TMS to immediately post-TMS treatment.
Time Frame 2 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
No data displayed because Outcome Measure has zero total analyzed. No participants were analyzed for this outcome measure.
Arm/Group Title Real TMS Sham TMS
Hide Arm/Group Description:

TMS will be administered using a 70-mm diameter air-cooled figure-of-8 coil and SuperRapid2 Magstim Stimulator. Repetitive pulses will be delivered to the right and left dorsolateral pre-frontal cortex (Brodmann area 46) using a frameless stereotactic navigation system and the subject's magnetic resonance imaging (MRI) in Brainsight software. Stimuli will be delivered at 20 Hz at 90% resting motor threshold (rMT) for 25 trains of 30 pulses per train, inter-train interval of 30 seconds for a total of 750 pulses per hemisphere. This dose and duration of repetitive TMS (rTMS) is based on physiological studies of healthy adults and treatment studies of cognition in PD and Alzheimer's disease.52, 123 Side of first stimulation (left vs right hemisphere) will be counterbalanced across subjects.

Real TMS: real treatment

Sham stimulation will be delivered using a sham coil fitted with electrodes to mimic both the auditory and somatic sensation of real TMS.

Sham TMS: placebo treatment

Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
2.Secondary Outcome
Title Post-TMS Change From Baseline in Cognitive Scores
Hide Description

Our behavioral outcome will be a change in the scores of the following tests:

Mattis Dementia Rating Scale: Higher raw scores = better cognitive status, ranging from 0 to 144. Normative data in healthy subjects range from 137 to 144.

Trail Making Test Trails B: average score is 75 seconds; deficient score is > 273 seconds.

Delis-Kaplan Executive Function System (DKEFS) - Verbal Fluency Test. Higher score = higher ability in language processing. Scales scores vary from 0 min to N/A max (no concrete maximum).

DKEFS - Stroop Interference Test measures inhibitory control and cognitive flexibility. Performance is measured by completion time. No min or max value for this test. Test should be discontinued after 90 sec.

For those, higher scores = higher abilities: California Verbal Learning Test (declarative memory, scale 0 to 80), Boston Naming Test (language, scale 0 to 60), Brief Test of Attention and Judgment of Line Orientation (scale 0 to 30)

Time Frame 2 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Real TMS Sham TMS
Hide Arm/Group Description:

TMS will be administered using a 70-mm diameter air-cooled figure-of-8 coil and SuperRapid2 Magstim Stimulator. Repetitive pulses will be delivered to the right and left dorsolateral pre-frontal cortex (Brodmann area 46) using a frameless stereotactic navigation system and the subject's magnetic resonance imaging (MRI) in Brainsight software. Stimuli will be delivered at 20 Hz at 90% resting motor threshold (rMT) for 25 trains of 30 pulses per train, inter-train interval of 30 seconds for a total of 750 pulses per hemisphere. This dose and duration of repetitive TMS (rTMS) is based on physiological studies of healthy adults and treatment studies of cognition in PD and Alzheimer's disease. Side of first stimulation (left vs right hemisphere) will be counterbalanced across subjects.

Real TMS: real treatment

Sham stimulation will be delivered using a sham coil fitted with electrodes to mimic both the auditory and somatic sensation of real TMS.

Sham TMS: placebo treatment

Overall Number of Participants Analyzed 22 24
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
Score on the Mattis Dementia Rating Scale (MDRS) at 2 weeks minus score on the MDRS at baseline -1.4  (4.55) 0  (5.55)
Score on the Verbal fluency at 2 weeks minus score on the Verbal fluency at baseline 0.3  (11.35) 1  (15.7)
Score on the Stroop Interference at 2 weeks minus score on the Stroop Interference at baseline -9.1  (18.55) -2.9  (18.85)
Score on the Brief Test of Attention (BTA) at 2 weeks minus score on the BTA at baseline -0.1  (4) 0.6  (4.15)
Score on the Boston Naming Test (BNT) at 2 weeks minus score on the BNT at baseline 0.2  (5.95) 1.4  (2.25)
Score on the Judgment of Line Orientation (JLO) at 2 weeks minus score on the JLO at baseline 0.9  (4.7) 1  (4.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Real TMS, Sham TMS
Comments We estimated a sample size of 20 per group would provide at least 80% power at a significance level of 0.05 to detect a between-group difference of 10 on the Matthis Dementia Rating Scale-2, an effect size similar to prior studies of rivastigmine.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1
Comments We determined whether there was a significant group difference between the real and sham treated PD-MCI patients on the DRS-2 change following rTMS using mixed model regression (MMR) to fit longitudinal models.
Method Mixed Models Analysis
Comments degrees of freedom: 46
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.07
Confidence Interval (2-Sided) 95%
-4.56 to 0.42
Estimation Comments [Not Specified]
Time Frame Adverse event data was collected throughout the study, i.e. 6 weeks.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Real TMS Sham TMS
Hide Arm/Group Description

TMS will be administered using a 70-mm diameter air-cooled figure-of-8 coil and SuperRapid2 Magstim Stimulator. Repetitive pulses will be delivered to the right and dorsolateral left pre-frontal cortex (Brodmann area 46) using a frameless stereotactic navigation system and the subject's magnetic resonance imaging (MRI) in Brainsight software. Stimuli will be delivered at 20 Hz at 90% resting motor threshold (rMT) for 25 trains of 30 pulses per train, inter-train interval of 30 seconds for a total of 750 pulses per hemisphere. This dose and duration of repetitive TMS (rTMS) is based on physiological studies of healthy adults and treatment studies of cognition in PD and Alzheimer's disease. Side of first stimulation (left vs right hemisphere) will be counterbalanced across subjects.

Real TMS: real treatment

Sham stimulation will be delivered using a sham coil fitted with electrodes to mimic both the auditory and somatic sensation of real TMS.

Sham TMS: placebo treatment

All-Cause Mortality
Real TMS Sham TMS
Affected / at Risk (%) Affected / at Risk (%)
Total   0/22 (0.00%)      0/24 (0.00%)    
Hide Serious Adverse Events
Real TMS Sham TMS
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/22 (4.55%)      0/24 (0.00%)    
Renal and urinary disorders     
Hospitalization *  1/22 (4.55%)  1 0/24 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Real TMS Sham TMS
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/22 (27.27%)      1/24 (4.17%)    
Blood and lymphatic system disorders     
vasovagal syncope *  1/22 (4.55%)  1 0/24 (0.00%)  0
Eye disorders     
mild blurry vision *  1/22 (4.55%)  1 0/24 (0.00%)  0
Infections and infestations     
mild flu *  1/22 (4.55%)  1 0/24 (0.00%)  0
Nervous system disorders     
motor problems *  0/22 (0.00%)  0 1/24 (4.17%)  1
confusion *  0/22 (0.00%)  0 1/24 (4.17%)  1
Psychiatric disorders     
hallucinations *  1/22 (4.55%)  1 0/24 (0.00%)  0
Skin and subcutaneous tissue disorders     
local pain *  1/22 (4.55%)  1 0/24 (0.00%)  0
Vascular disorders     
burst vein in eye *  1/22 (4.55%)  1 0/24 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
Our specialized MEG data analyst working on the Primary outcome has encountered a Covid-related family emergency, which has delayed the analysis process.
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: Isabelle Buard, PhD
Organization: University of Colorado Denver - Anschutz Medical Campus
Phone: (303)724-5973
EMail: Isabelle.Buard@cuanschutz.edu
Layout table for additonal information
Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT02346708    
Other Study ID Numbers: 13-2724
1K02NS080885-01A1 ( U.S. NIH Grant/Contract )
First Submitted: January 9, 2015
First Posted: January 27, 2015
Results First Submitted: April 6, 2020
Results First Posted: December 9, 2020
Last Update Posted: December 9, 2020