Trial Outcomes & Findings for Cognitive Dysfunction in Parkinson's Disease (NCT NCT02346708)
NCT ID: NCT02346708
Last Updated: 2021-02-09
Results Overview
Our MEG outcome will be a change in small-worldness, global efficiency, nodal efficiency and degree distribution pre-TMS to immediately post-TMS treatment.
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
49 participants
Primary outcome timeframe
2 weeks
Results posted on
2021-02-09
Participant Flow
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.
70 participants were assessed for eligibility (following Inclusion and exclusion criteria), 21 were screen failures, 49 participants were randomized to treatment.
Participant milestones
| Measure |
Real TMS
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 TMS
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 Study
STARTED
|
24
|
25
|
|
Overall Study
COMPLETED
|
22
|
24
|
|
Overall Study
NOT COMPLETED
|
2
|
1
|
Reasons for withdrawal
| Measure |
Real TMS
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 TMS
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 Study
Adverse Event
|
2
|
0
|
|
Overall Study
Protocol Violation
|
0
|
1
|
Baseline Characteristics
Cognitive Dysfunction in Parkinson's Disease
Baseline characteristics by cohort
| Measure |
Real TMS
n=22 Participants
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 TMS
n=24 Participants
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
n=46 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
8 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
14 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
31 Participants
n=5 Participants
|
|
Age, Continuous
|
67.4 years
STANDARD_DEVIATION 7.2 • n=5 Participants
|
69.5 years
STANDARD_DEVIATION 8 • n=7 Participants
|
68.5 years
STANDARD_DEVIATION 7.6 • n=5 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
16 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
33 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
20 Participants
n=5 Participants
|
24 Participants
n=7 Participants
|
44 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
22 participants
n=5 Participants
|
24 participants
n=7 Participants
|
46 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 2 weeksPopulation: No data displayed because Outcome Measure has zero total analyzed. No participants were analyzed for this outcome measure.
Our MEG outcome will be a change in small-worldness, global efficiency, nodal efficiency and degree distribution pre-TMS to immediately post-TMS treatment.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 2 weeksOur 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)
Outcome measures
| Measure |
Real TMS
n=22 Participants
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 TMS
n=24 Participants
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
|
|---|---|---|
|
Post-TMS Change From Baseline in Cognitive Scores
Score on the Brief Test of Attention (BTA) at 2 weeks minus score on the BTA at baseline
|
-0.1 Scores on a scale
Standard Deviation 4
|
0.6 Scores on a scale
Standard Deviation 4.15
|
|
Post-TMS Change From Baseline in Cognitive Scores
Score on the Mattis Dementia Rating Scale (MDRS) at 2 weeks minus score on the MDRS at baseline
|
-1.4 Scores on a scale
Standard Deviation 4.55
|
0 Scores on a scale
Standard Deviation 5.55
|
|
Post-TMS Change From Baseline in Cognitive Scores
Score on the Verbal fluency at 2 weeks minus score on the Verbal fluency at baseline
|
0.3 Scores on a scale
Standard Deviation 11.35
|
1 Scores on a scale
Standard Deviation 15.7
|
|
Post-TMS Change From Baseline in Cognitive Scores
Score on the Stroop Interference at 2 weeks minus score on the Stroop Interference at baseline
|
-9.1 Scores on a scale
Standard Deviation 18.55
|
-2.9 Scores on a scale
Standard Deviation 18.85
|
|
Post-TMS Change From Baseline in Cognitive Scores
Score on the Boston Naming Test (BNT) at 2 weeks minus score on the BNT at baseline
|
0.2 Scores on a scale
Standard Deviation 5.95
|
1.4 Scores on a scale
Standard Deviation 2.25
|
|
Post-TMS Change From Baseline in Cognitive Scores
Score on the Judgment of Line Orientation (JLO) at 2 weeks minus score on the JLO at baseline
|
0.9 Scores on a scale
Standard Deviation 4.7
|
1 Scores on a scale
Standard Deviation 4.2
|
Adverse Events
Real TMS
Serious events: 1 serious events
Other events: 6 other events
Deaths: 0 deaths
Sham TMS
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Real TMS
n=22 participants at risk
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 TMS
n=24 participants at risk
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
|
|---|---|---|
|
Renal and urinary disorders
Hospitalization
|
4.5%
1/22 • Number of events 1 • Adverse event data was collected throughout the study, i.e. 6 weeks.
|
0.00%
0/24 • Adverse event data was collected throughout the study, i.e. 6 weeks.
|
Other adverse events
| Measure |
Real TMS
n=22 participants at risk
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 TMS
n=24 participants at risk
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
|
|---|---|---|
|
Blood and lymphatic system disorders
vasovagal syncope
|
4.5%
1/22 • Number of events 1 • Adverse event data was collected throughout the study, i.e. 6 weeks.
|
0.00%
0/24 • Adverse event data was collected throughout the study, i.e. 6 weeks.
|
|
Skin and subcutaneous tissue disorders
local pain
|
4.5%
1/22 • Number of events 1 • Adverse event data was collected throughout the study, i.e. 6 weeks.
|
0.00%
0/24 • Adverse event data was collected throughout the study, i.e. 6 weeks.
|
|
Psychiatric disorders
hallucinations
|
4.5%
1/22 • Number of events 1 • Adverse event data was collected throughout the study, i.e. 6 weeks.
|
0.00%
0/24 • Adverse event data was collected throughout the study, i.e. 6 weeks.
|
|
Nervous system disorders
motor problems
|
0.00%
0/22 • Adverse event data was collected throughout the study, i.e. 6 weeks.
|
4.2%
1/24 • Number of events 1 • Adverse event data was collected throughout the study, i.e. 6 weeks.
|
|
Eye disorders
mild blurry vision
|
4.5%
1/22 • Number of events 1 • Adverse event data was collected throughout the study, i.e. 6 weeks.
|
0.00%
0/24 • Adverse event data was collected throughout the study, i.e. 6 weeks.
|
|
Nervous system disorders
confusion
|
0.00%
0/22 • Adverse event data was collected throughout the study, i.e. 6 weeks.
|
4.2%
1/24 • Number of events 1 • Adverse event data was collected throughout the study, i.e. 6 weeks.
|
|
Vascular disorders
burst vein in eye
|
4.5%
1/22 • Number of events 1 • Adverse event data was collected throughout the study, i.e. 6 weeks.
|
0.00%
0/24 • Adverse event data was collected throughout the study, i.e. 6 weeks.
|
|
Infections and infestations
mild flu
|
4.5%
1/22 • Number of events 1 • Adverse event data was collected throughout the study, i.e. 6 weeks.
|
0.00%
0/24 • Adverse event data was collected throughout the study, i.e. 6 weeks.
|
Additional Information
Isabelle Buard, PhD
University of Colorado Denver - Anschutz Medical Campus
Phone: (303)724-5973
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place