Transcranial Magnetic Stimulation for Apathy in Mild Cognitive Impairment (TAMCI)

• ClinicalTrials.gov Identifier: NCT03590327
• Recruitment Status: Recruiting
• First Posted: July 18, 2018
• Last Update Posted: July 15, 2020
• Sponsor: VA Office of Research and Development
• Collaborators: Central Arkansas Veterans Healthcare System; University of Arkansas
• Information provided by (Responsible Party): VA Office of Research and Development

Tracking Information

• First Submitted Date: May 15, 2018
• First Posted Date: July 18, 2018
• Last Update Posted Date: July 15, 2020
• Actual Study Start Date: November 1, 2018
• Estimated Primary Completion Date: September 30, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 5, 2018)

Change in Apathy Evaluation Scale Score [ Time Frame: 2 weeks, 6 weeks, 6 months, 12 months, 24 months, 36 months, and 48 months ]

Range 18-72 Lower score is improvement

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 5, 2018)

• Change in Modified Mini Mental State Examination Score [ Time Frame: 2 weeks, 6 weeks, 6 months, 12 months, 24 months, 36 months, and 48 months ]
  Range 0-100 Higher score is improvement
• Change in Conner's Continuous Performance Test Commission Error percentage [ Time Frame: 2 weeks, 6 weeks, 6 months, 12 months, 24 months, 36 months, and 48 months ]
  Range 0-100% Higher score is improvement

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Transcranial Magnetic Stimulation for Apathy in Mild Cognitive Impairment
• Official Title: Transcranial Magnetic Stimulation for Apathy in Mild Cognitive Impairment
• Brief Summary: Apathy, a profound loss of initiative and motivation, is often seen in older Veterans with memory problems. Apathy leads to serious health problems, increases dependency, and caregiver burden. If untreated, apathy hastens the progression to frank dementia. In a pilot study, the investigators found that apathy, working memory, and function can be restored using magnetic stimulation in some but not all older Veterans. The reason for this variation is unknown. The investigators propose a three-phase study in 125 older Veterans with mild memory problems. Their motivation, memory, and function will be measured periodically. Veterans with apathy that are eligible for treatment will receive either real or sham magnetic stimulation to the front part of their brain over 20 sessions. Genetic testing and biomarkers will be used to differentiate those who respond to magnetic stimulation from those who do not. Impact on function, quality of life, and rates of progression to dementia will also be studied.
• Detailed Description: Apathy, a profound loss of initiative and motivation, is often seen in older Veterans with memory problems. Apathy leads to serious health problems, increases dependency, and caregiver burden. If untreated, apathy hastens the progression to frank dementia. In a pilot study, the investigators found that apathy, working memory, and function can be restored using magnetic stimulation in some but not all older Veterans. The reason for this variation is unknown. The investigators propose a three-phase study in 125 older Veterans with mild cognitive impairment. Their motivation, other behavioral problems, memory, and function will be measured periodically. Veterans with apathy that are eligible for treatment will receive either real or sham magnetic stimulation to the dorsolateral prefrontal cortex over 20 daily sessions on consecutive week days. Genetic testing and biomarkers will be used to differentiate those who respond to magnetic stimulation from those who do not. Impact on function, quality of life, and rates of progression to dementia will also be studied.
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• Apathy
• Mild Cognitive Impairment
• Transcranial Magnetic Stimulation

Intervention

Device: Transcranial Magnetic Stimulation

rTMS

Study Arms

• No Intervention: Apathy +, rTMS -
  This arm will be followed without intervention
• Active Comparator: rTMS
  This group will be randomized to receive rTMS treatment
  Intervention: Device: Transcranial Magnetic Stimulation
• Sham Comparator: Sham
  This group will be randomized to receive sham treatment
  Intervention: Device: Transcranial Magnetic Stimulation

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: July 5, 2018): 125
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: September 30, 2023
• Estimated Primary Completion Date: September 30, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• meeting the modified Mayo Clinic criteria for MCI
• Having caregivers
• apathy threshold (NPI)
• MMSE 23
• On stable dose of antidepressants for at least a month (if applicable)

Exclusion Criteria:

PHASE I

• Uncontrolled diabetes mellitus (Fasting BS>200mg/dl, HbA1c>10)
• Renal disease requiring dialysis
• Uncontrolled blood pressure (>160/100, <100 systolic)
• Metastatic cancer or undergoing chemotherapy
• Deep venous thrombosis or myocardial infarction in past 3 months
• Uncontrolled malignant cardiac arrhythmia
• Cerebral aneurysm or intracranial bleed in past year
• Unstable angina in past month
• Unstable abdominal or thoracic aortic aneurysm (>4cm)
• End-stage congestive heart failure

EXCLUSIONARY DUE TO rTMS: ALL PHASE II AND SUBSET OF PHASE I THAT RECEIVE SINGLE SESSION rTMS

• Taking medications known to increase risk of seizures from 2012 Beers criteria such as bupropion, chlorpromazine, clozapine.
• Taking other medications known to increase risk of seizures such as tricyclic antidepressants.
• Taking ototoxic medications: Aminoglycosides, Cisplatin
• History of seizures/ seizures in first degree relatives
• Those with implanted device
• History of stroke, aneurysm, or cranial neurosurgery
• History of bipolar disorder
• Current alcohol related disorder needing medical treatment
• History of Tourette's syndrome or presence of motor tics
• History of abnormal electroencephalogram (EEG)

EXCLUSIONARY DUE TO CONFOUNDING WITH APATHY: PHASE II

• Current episode of Major Depressive Disorder
• Current use of stimulants
• Change in dose of dementia medications within 30 days
• Change in dose of antidepressants within 30 days

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 55 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: Prasad R Padala, MBBS; (501) 257-2537; Prasad.Padala@va.gov

Contact: Christopher M Parkes, BS; (501) 257-2504; christopher.parkes@va.gov

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03590327
• Other Study ID Numbers: D2638-R; 1115904 ( Other Identifier: Central Arkansas Veterans Healthcare System )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: Yes

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: VA Office of Research and Development
• Study Sponsor: VA Office of Research and Development

Collaborators

• Central Arkansas Veterans Healthcare System
• University of Arkansas

Investigators

• Principal Investigator: Prasad R. Padala, MBBS; Central Arkansas Veterans Healthcare System Eugene J. Towbin Healthcare Center, Little Rock, AR

• PRS Account: VA Office of Research and Development
• Verification Date: July 2020