Transcranial Magnetic Stimulation for Apathy in Mild Cognitive Impairment

Mild Cognitive Impairment Clinical Trial

— TAMCI  

Official title:

Transcranial Magnetic Stimulation for Apathy in Mild Cognitive Impairment

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03590327
• Other study ID #: D2638-R
• Secondary ID: 1115904
• Status: Recruiting
• Phase: N/A
• Start date: November 1, 2018
• Est. completion date: October 31, 2024

Study information

• Verified date: December 2023
• Source: VA Office of Research and Development
• Contact: Prasad R Padala, MBBS MBBS
• Phone: (501) 257-2537
• Email: Prasad.Padala[@]va.gov
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

A project modification was obtained to conduct a cross-sectional study, the COVID Dementia study. The cross-sectional study will examine the effect of the pandemic on MCI and AD patients and their caregivers ("individual COVID-related factors" such as, personally infected, death of a friend/family member, economic hardship, disruption in care, isolation), barriers to telehealth, caregiver distress, NPS, cognition (including onset of delirium), and function. Our goal is to develop a multi-pronged, remotely deliverable intervention to address consequences of healthcare disruptions in older Veterans with cognitive impairment.

Aim 1. To explore the association between COVID-related factors and neuropsychiatric symptoms in individuals with MCI and AD. Hypothesis: The number of COVID-related factors endorsed by caregivers will be positively correlated with the severity of NPI-Q in individuals with MCI and AD.

Aim 2. To assess cognition (telephonic version of the Montreal Cognitive Assessment; tMoCA12, and daily function (Functional Activities Questionnaire; FAQ13). Hypothesis: The number of COVID-related factors will be positively correlated with the severity of cognitive and functional deficits in individuals with MCI and AD.

Aim 3. To explore the associations among COVID-related factors and caregiver distress. Hypothesis: Caregiver resilience and perceived social support will modify the association between COVID-related factors and severity of distress in caregivers.

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.

A project modification was obtained to conduct a cross-sectional study, the COVID Dementia study. The cross-sectional study will examine the effect of the pandemic on MCI and AD patients and their caregivers ("individual COVID-related factors" such as, personally infected, death of a friend/family member, economic hardship, disruption in care, isolation), barriers to telehealth, caregiver distress, NPS, cognition (including onset of delirium), and function. Our goal is to develop a multi-pronged, remotely deliverable intervention to address consequences of healthcare disruptions in older Veterans with cognitive impairment.

Aim 1. To explore the association between COVID-related factors and neuropsychiatric symptoms in individuals with MCI and AD. Hypothesis: The number of COVID-related factors endorsed by caregivers will be positively correlated with the severity of NPI-Q in individuals with MCI and AD.

Aim 2. To assess cognition (telephonic version of the Montreal Cognitive Assessment; tMoCA12, and daily function (Functional Activities Questionnaire; FAQ13). Hypothesis: The number of COVID-related factors will be positively correlated with the severity of cognitive and functional deficits in individuals with MCI and AD.

Aim 3. To explore the associations among COVID-related factors and caregiver distress. Hypothesis: Caregiver resilience and perceived social support will modify the association between COVID-related factors and severity of distress in caregivers.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 125
• Est. completion date: October 31, 2024
• Est. primary completion date: October 31, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 55 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Apathy
• Cognitive Dysfunction
• COVID
• Loneliness
• Mild Cognitive Impairment
• Neuropsychiatric Symptoms
• Transcranial Magnetic Stimulation

Intervention

Device:
• Transcranial Magnetic Stimulation
rTMS

Locations

Country	Name	City	State
United States	Central Arkansas Veterans Healthcare System Eugene J. Towbin Healthcare Center, Little Rock, AR	North Little Rock	Arkansas

Sponsors (3)

Lead Sponsor	Collaborator
VA Office of Research and Development	Central Arkansas Veterans Healthcare System, University of Arkansas

Country where clinical trial is conducted

United States, 

References & Publications (9)

Mintzer J, Lanctot KL, Scherer RW, Rosenberg PB, Herrmann N, van Dyck CH, Padala PR, Brawman-Mintzer O, Porsteinsson AP, Lerner AJ, Craft S, Levey AI, Burke W, Perin J, Shade D; ADMET 2 Research Group. Effect of Methylphenidate on Apathy in Patients With Alzheimer Disease: The ADMET 2 Randomized Clinical Trial. JAMA Neurol. 2021 Nov 1;78(11):1324-1332. doi: 10.1001/jamaneurol.2021.3356. — View Citation

Mortby ME, Adler L, Aguera-Ortiz L, Bateman DR, Brodaty H, Cantillon M, Geda YE, Ismail Z, Lanctot KL, Marshall GA, Padala PR, Politis A, Rosenberg PB, Siarkos K, Sultzer DL, Theleritis C; ISTAART NPS PIA. Apathy as a Treatment Target in Alzheimer's Disease: Implications for Clinical Trials. Am J Geriatr Psychiatry. 2022 Feb;30(2):119-147. doi: 10.1016/j.jagp.2021.06.016. Epub 2021 Jul 1. — View Citation

Okolichany R, Padala PR, Mooney S. Cognitive and Functional Abilities in an Older Adult Veteran Before and After Contracting COVID-19. J Alzheimers Dis Rep. 2022 Mar 25;6(1):115-120. doi: 10.3233/ADR-210055. eCollection 2022. — View Citation

Padala KP, Jendro AM, Wilson KB, Padala PR. Technology Use to Bridge the Gap of Social Distancing during COVID-19. J Geriatr Med Gerontol. 2020 Jun 29;6(2):10.23937/2469-5858/1510092. doi: 10.23937/2469-5858/1510092. No abstract available. — View Citation

Padala KP, Parkes CM, Padala PR. Neuropsychological and Functional Impact of COVID-19 on Mild Cognitive Impairment. Am J Alzheimers Dis Other Demen. 2020 Jan-Dec;35:1533317520960875. doi: 10.1177/1533317520960875. — View Citation

Padala PR, Boozer EM, Lensing SY, Parkes CM, Hunter CR, Dennis RA, Caceda R, Padala KP. Neuromodulation for Apathy in Alzheimer's Disease: A Double-Blind, Randomized, Sham-Controlled Pilot Study. J Alzheimers Dis. 2020;77(4):1483-1493. doi: 10.3233/JAD-200640. — View Citation

Preston AM, Brown L, Padala KP, Padala PR. Veterans Affairs Health Care Provider Perceptions of Virtual Reality: Brief Exploratory Survey. Interact J Med Res. 2022 Sep 2;11(2):e38490. doi: 10.2196/38490. — View Citation

Preston AM, Padala PR. Virtual reality on the verge of becoming a reality for geriatric research. Int Psychogeriatr. 2022 Feb;34(2):97-99. doi: 10.1017/S1041610221000867. Epub 2021 Jun 8. No abstract available. — View Citation

Sharma T, Padala PR, Mehta JL. Loneliness and Social Isolation: Determinants of Cardiovascular Outcomes. Curr Cardiol Rev. 2021;17(6):e051121190873. doi: 10.2174/1573403X17666210129101845. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Neuropsychiatric Inventory - Questionnaire	To study the impact of COVID pandemic on neuropsychiatric symptoms of dementia. This outcome measure has questions pertaining to twelve neuropsychiatric symptoms seen in dementia. An aggregate score of the symptoms, caregiver distress and change during the COVID pandemic will be reported.; Presence or lack of each domain is reported for this study. No range in score for this scale.	Through study completion, an average of 1 year
Other	Functional Activities Questionnaire	Measure of functional independence Range: 0-30 Higher score indicates higher dependence	Through study completion, an average of 1 year
Other	UCLA Loneliness scale	Measures loneliness Range 3-9 Higher score indicates higher loneliness	Through study completion, an average of 1 year
Other	T-MoCA	Measures global cognition Range: 0-22 Higher scores indicate better cognition	Through study completion, an average of 1 year
Primary	Change in Apathy Evaluation Scale Score	Range 18-72 Lower score is improvement	2 weeks, 6 weeks, 6 months, 12 months, 24 months, 36 months, and 48 months
Secondary	Change in Modified Mini Mental State Examination Score	Range 0-100 Higher score is improvement	2 weeks, 6 weeks, 6 months, 12 months, 24 months, 36 months, and 48 months
Secondary	Change in Conner's Continuous Performance Test Commission Error percentage	Range 0-100% Higher score is improvement	2 weeks, 6 weeks, 6 months, 12 months, 24 months, 36 months, and 48 months