Repetitive Transcranial Magnetic Stimulation for Apathy Treatment in Alzheimer's Disease

Repetitive Transcranial Magnetic Stimulation for Apathy Treatment in Alzheimer's Disease: a Randomised, Double-blind, Controlled Study

We aim to evaluate the safety and efficacy of repetitive transcranial magnetic stimulation (rTMS) for apathy treatment in patients with Alzheimer's disease (AD). We hypothesize that rTMS will be superior to placebo to reduce apathy symptoms and severity in patients with AD.

Study Overview

• Status: Unknown
• Conditions: Alzheimer's Disease; Apathy
• Intervention / Treatment: Device: Magnetic Stimulator Magstim Rapid 2; Device: Sham Magnetic Stimulator

Detailed Description

This study aims to enroll 40 patients with mild and moderate Alzheimer's disease with apathy symptoms that will be randomized to receive rTMS or sham procedure. Subjects will be randomized in two arms (rTMS or sham procedure) in 1:1 proportion.

Eligibility criteria:

• Diagnosis of Alzheimer's disease, mild and moderate stage (MMSE range from 10 to 20);
• Diagnosis of apathy;
• age between 60 and 85 years-old;
• On stable doses of cholinesterase inhibitors (donepezil, rivastigmine, galantamine) or memantine for at least 6 months prior to enrollment;

The primary outcome measures is the Apathy Inventoire. Secondary outcome measures are the NPI score, ADAS-cog scores and the Zarit Burden Scale scores.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Breno S Diniz, MD, PhD; Phone Number: +55 31 97950860; Email: brenosatler@gmail.com

Study Locations

• Brazil
  • Outside of U.S.
    • Belo Horizonte, Outside of U.S., Brazil, 30130-100
      • Recruiting
      • Federal University of Minas Gerais
      • Principal Investigator: Breno S Diniz, MD, PhD
      • Contact: Marco A Romano-Silva, MD, PhD; Phone Number: +55 31 3409-9785; Email: romanosilva@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age between 60 to 85 years-old
• Mild or moderate Alzheimer's disease (MMSE scores between 10 and 20)
• Apathy diagnosis
• On stable doses of cholinesterase inhibitors (donepezil, galantamine, rivastigmine) and/or memantine for at least 6 months prior to enrollment

Exclusion Criteria:

• history of epilepsy or convulsions
• History of migraine or headaches episodes twice per week or more
• History of neurodegenerative diseases other than Alzheimer's disease
• Current use of first generation antipsychotics, clozapine, tricyclic drugs or anticonvulsants
• History of cerebral ischemic episode

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Repetitive TMS; Patients will receive 10 consecutive sessions of repetitive transcranial magnetic stimulation with the following protocol: Frequency: 10 Hz Intensity: 90% motor limiar Session duration: 16 minutes (20 sequencies of 6 seconds of stimulation followed by intervals of 30 seconds); Localization: Left pre-frontal dorsolateral cortex;	Device: Magnetic Stimulator Magstim Rapid 2; All procedures will use the Magnetic Stimulator Magstim Rapid 2. Total of session: 10 rTMS protocol: Freqüency: 10 Hz Intensity: 90% limiar motor Session duration: 16 minutes (20 TMS sequences of 6 second with intervals of 30 seconds between each sequence) Location: Left dorsolateral pre-frontal cortex; Other Names: rTMS
Sham Comparator: Sham TMS; Patients will receive 10 consecutive sessions of sham transcranial magnetic stimulation following the same protocol as the intervention arm, but with no magnetic stimulation of the brain.	Device: Sham Magnetic Stimulator; This intervention will follow the same protocol of the rTMS except that subjects will not receive magnetic stimulation of the brain. Total of session: 10; Other Names: Sham

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in apathy symptoms	Reduction of 30% in the Apathy Inventoire scores between baseline and 12 weeks after treatment.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in ADAS-Cog scores	Improvement in ADAS-Cog scores between baseline and 12 weeks after treatment.	12 weeks
Change in the Zarit Burden Scale	Reduction in the Zarit Burden Scale between baseline and 12 weeks after treatment.	12 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety assessment	Assessment of rTMS safety by the UKU scale.	4th week, 8th week, 12th week

Collaborators and Investigators

• Sponsor: Federal University of Minas Gerais
• Investigators: Principal Investigator: Breno S Diniz, MD, PhD, Federal University of Minas Gerais

Study record dates

Study Major Dates

• Study Start: June 1, 2013
• Primary Completion (Anticipated): December 1, 2014
• Study Completion (Anticipated): December 1, 2015

Study Registration Dates

• First Submitted: June 18, 2013
• First Submitted That Met QC Criteria: June 24, 2013
• First Posted (Estimate): June 25, 2013

Study Record Updates

• Last Update Posted (Estimate): June 25, 2013
• Last Update Submitted That Met QC Criteria: June 24, 2013
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Keywords: Apathy; Alzheimer's disease; Cognition; Burden of Care
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: CAAE: 15388913.6.0000.5149