Study on the Effect of Transcranial Magnetic Stimulation in Mild to Moderate Alzheimer's Disease

Mild to Moderate Alzheimer Disease Clinical Trial

Official title:

Prospective, Randomized, Evaluator-blind, Single Center Study on the Effect of Transcranial Magnetic Stimulation in Mild to Moderate Alzheimer's Disease

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04260724
• Other study ID #: SMC_2019-04-010-004
• Status: Not yet recruiting
• Phase: N/A
• Start date: February 7, 2020
• Est. completion date: February 7, 2022

Study information

• Verified date: February 2020
• Source: Samsung Medical Center
• Contact: Young Hee Jung, MD PhD
• Phone: 82-10-6755-5462
• Email: neophilia1618[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The investigators will compare cognitition, mood (depression), ADL, and brain structural and functional MRI before and after 4-week transcranial magnetic stimulation in patients with mild to moderate Alzheimer's disease.

The investigators also compare the change of cognitition, mood (depression), ADL, and brain structural and functional MRI between TMS group and sham coil group.

Description:

Each 16 patients will be allocated to TMS group and sham coil group. Before TMS/sham coil stimulation, the investigators will take fMRI of each patient, and figure out which focus has strongest connectivity to hippocampus among lateral parietal regions of the brain. The investigators will fix the TSM transduced and apply accurate TMS stimulation to the focus using personalized frames. The investigators will make the frame using 3D printing technology.

After 4 week- TMS stimulation, the investigators will compare cognitition, mood (depression), ADL, and brain structural and functional MRI beween baseline and after intervention. The investigators also compare the change of cognitition, mood (depression), ADL, and brain structural and functional MRI between TMS group and sham coil group.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 32
• Est. completion date: February 7, 2022
• Est. primary completion date: February 7, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years to 90 Years

Eligibility

Inclusion Criteria:

• patients who visited memory clinic of Samsung Medical Center

• aged 55 ~ 90

• diagnosed as probable Alzheimer dementia according to NIA-AA guideline 2011, or MCI patiens with amyloid PET positivity

• below -1SD in SVLTdelayed recall test and RCFT delayed recall test

• K-MMSE >=18

• no epileptic discharge in EEG

• no history of epilepsy

• no arrhythmia or MI in ECG

• can read and write Korean (literate)

• volunteer and agree to the registration

Exclusion Criteria:

• no other neurologic deficit which can cause dementia except for Alzheimer's disease

• paitient who has severe cerebral white matter hyperintensities. (deep white matter >=2.5cm and caps or band >=1.0 cm)

• patients with severe medical disease including caner and ishemic heart disease

• claustrophobia or allergic to contrast of MRI

• medical deviced which is not removable (e.g pacemaker, cochlear implantation, dental prosthesis)

• history of brain surgery, and intervension or surgery of intra/extracranial artery(e.g. carotid artery stent insertion, CEA)

• patient with dyspnea during resting

• history of loss of consciousness for more than 1 hour except for general anesthesia

• patients who cannot read written material because of poor visual acuity

• patients who cannot communicate because of severe hearing difficulty

• history of ototoxicity medication or exposure severe noises

• determined as inapropriate to participate clinical trial

Related Conditions & MeSH terms

• Alzheimer Disease
• Mild to Moderate Alzheimer Disease

Intervention

Device:
• TMS
stimulation intensity : motor threshold 100% stimulation frequency : 1600 pulses for 20 minutes stimulation duration :for four weaks, 20 minutes/day, 5 days per week (Monday - Friday )
• sham coil stimulation
no stimulation Although the sound from device during stimulation is similar, no stimulation is applied.

Locations

Country	Name	City	State
Korea, Republic of	Samsung Medical Center	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Samsung Medical Center

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (10)

Bondi MW, Edmonds EC, Jak AJ, Clark LR, Delano-Wood L, McDonald CR, Nation DA, Libon DJ, Au R, Galasko D, Salmon DP. Neuropsychological criteria for mild cognitive impairment improves diagnostic precision, biomarker associations, and progression rates. J Alzheimers Dis. 2014;42(1):275-89. doi: 10.3233/JAD-140276. — View Citation

Cotelli M, Calabria M, Manenti R, Rosini S, Zanetti O, Cappa SF, Miniussi C. Improved language performance in Alzheimer disease following brain stimulation. J Neurol Neurosurg Psychiatry. 2011 Jul;82(7):794-7. doi: 10.1136/jnnp.2009.197848. Epub 2010 Jun 23. — View Citation

Cotelli M, Manenti R, Cappa SF, Geroldi C, Zanetti O, Rossini PM, Miniussi C. Effect of transcranial magnetic stimulation on action naming in patients with Alzheimer disease. Arch Neurol. 2006 Nov;63(11):1602-4. — View Citation

Cotelli M, Manenti R, Cappa SF, Zanetti O, Miniussi C. Transcranial magnetic stimulation improves naming in Alzheimer disease patients at different stages of cognitive decline. Eur J Neurol. 2008 Dec;15(12):1286-92. doi: 10.1111/j.1468-1331.2008.02202.x. — View Citation

Kim S, Nilakantan AS, Hermiller MS, Palumbo RT, VanHaerents S, Voss JL. Selective and coherent activity increases due to stimulation indicate functional distinctions between episodic memory networks. Sci Adv. 2018 Aug 22;4(8):eaar2768. doi: 10.1126/sciadv — View Citation

Koch G, Bonnì S, Pellicciari MC, Casula EP, Mancini M, Esposito R, Ponzo V, Picazio S, Di Lorenzo F, Serra L, Motta C, Maiella M, Marra C, Cercignani M, Martorana A, Caltagirone C, Bozzali M. Transcranial magnetic stimulation of the precuneus enhances memory and neural activity in prodromal Alzheimer's disease. Neuroimage. 2018 Apr 1;169:302-311. doi: 10.1016/j.neuroimage.2017.12.048. Epub 2017 Dec 19. — View Citation

Nilakantan AS, Mesulam MM, Weintraub S, Karp EL, VanHaerents S, Voss JL. Network-targeted stimulation engages neurobehavioral hallmarks of age-related memory decline. Neurology. 2019 May 14;92(20):e2349-e2354. doi: 10.1212/WNL.0000000000007502. Epub 2019 Apr 17. — View Citation

Ridding MC, Rothwell JC. Is there a future for therapeutic use of transcranial magnetic stimulation? Nat Rev Neurosci. 2007 Jul;8(7):559-67. Review. — View Citation

Wang JX, Rogers LM, Gross EZ, Ryals AJ, Dokucu ME, Brandstatt KL, Hermiller MS, Voss JL. Targeted enhancement of cortical-hippocampal brain networks and associative memory. Science. 2014 Aug 29;345(6200):1054-7. doi: 10.1126/science.1252900. — View Citation

Weissman MM, Myers JK, Tischler GL, Holzer CE 3rd, Leaf PJ, Orvaschel H, Brody JA. Psychiatric disorders (DSM-III) and cognitive impairment among the elderly in a U.S. urban community. Acta Psychiatr Scand. 1985 Apr;71(4):366-79. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	the short term change of K-MMSE score in TMS group	the short term change of K-MMSE (Korean version of mini mental status exam) score in TMS group	4 weeks
Primary	the short term change of K-MoCA score in TMS group	the short term change of K-MoCA (Korean version of Montreal cognitive assessment) score in TMS group	4 weeks
Primary	the short term change of ADAS-Cog score in TMS group	the short term change of ADAS-Cog(the Alzheimer's disease assessment scale-cognitive subscale) score in TMS group	4 weeks
Primary	the short term change of COWAT score in TMS group	the short term change of COWAT(controlled oral word association) score in TMS group	4 weeks
Primary	the short term change of Stroop score in TMS group	the short term change of Stroop score in TMS group	4 weeks
Primary	the short term change of TMT score in TMS group	the short term change of TMT(trail-making test) score in TMS group	4 weeks
Primary	the short term change of RVP score in TMS group	the short term change of RVP(raid visual information processing) score in TMS group	4 weeks
Primary	the short term change of SWM score in TMS group	the short term change of SWM (spatial working memory) score in TMS group	4 weeks
Primary	the short term change of PRM score in TMS group	the short term change of PRM(pattern recognition memory) score in TMS group	4 weeks
Secondary	the long term change of K-MMSE score in TMS group	the long term change of K-MMSE (Korean version of mini mental status exam) score in TMS group	8 weeks
Secondary	the long term change of K-MoCA score in TMS group	the long term change of K-MoCA (Korean version of Montreal cognitive assessment) score in TMS group	8 weeks
Secondary	the long term change of ADAS-Cog score in TMS group	the long term change of ADAS-Cog(the Alzheimer's disease assessment scale-cognitive subscale) score in TMS group	8 weeks
Secondary	the long term change of COWAT score in TMS group	the long term change of COWAT(controlled oral word association) score in TMS group	8 weeks
Secondary	the long term change of Stroop score in TMS group	the long term change of Stroop score in TMS group	8 weeks
Secondary	the long term change of TMT score in TMS group	the long term change of TMT(trail-making test) score in TMS group	8 weeks
Secondary	the long term change of RVP score in TMS group	the long term change of RVP(raid visual information processing) score in TMS group	8 weeks
Secondary	the long term change of SWM score in TMS group	the long term change of SWM (spatial working memory) score in TMS group	8 weeks
Secondary	the long term change of PRM score in TMS	the long term change of PRM(pattern recognition memory) score in TMS group	8 weeks
Secondary	the change of ADL(activity of daily life) in TMS group	the score change of S-IADL(Seoul-Instrumental activities of daily life)	4 weeks
Secondary	the short term change of mood (depression) in TMS group	the score change of GDS(geriatric depression scale) short form	4 weeks
Secondary	the long term change of mood (depression) in TMS group	the score change of GDS(geriatric depression scale) short form	8 weeks
Secondary	the change of brain function in TMS group	the qualititve change of resting functional MRI	4 weeks
Secondary	the change of brain structure in TMS group	the change of FA (fractional anisotropy) value in DTI (diffusion tensor imaging) analysis	4 weeks
Secondary	the comparison of short term change of K-MMSE score between TMS group and sham group	the score change of K-MMSE (Korean version of mini mental status exam)	4 weeks
Secondary	the comparison of short term change of K-MoCA score between TMS group and sham group	the score change of K-MoCA (Korean version of Montreal cognitive assessment)	4 weeks
Secondary	the comparison of short term change of CDR-SOB between TMS group and sham group	the score change of CDR-SOB (Clinical dementia rating-sum of boxes)	4 weeks
Secondary	the comparison of short term change of ADAS-Cog between TMS group and sham group	the score change of ADAS-Cog ( the Alzheimer's disease assessment scale-cognitive subscale)	4 weeks
Secondary	the comparison of short term change of COWAT score between TMS group and sham group	the score change of COWAT(controlled oral word association) score	4 weeks
Secondary	the comparison of short term change of Stroop test score between TMS group and sham group	the score change of Stroop test score	4 weeks
Secondary	the comparison of short term change of TMT between TMS group and sham group	the score change of TMT (trail making test)	4 weeks
Secondary	the comparison of short term change of RVP score between TMS group and sham group	the score change of RVP(raid visual information processing) score	4 weeks
Secondary	the comparison of short term change of SWM between TMS group and sham group	the score change of SWM (spatial working memory) score	4 weeks
Secondary	the comparison of short term change of PRM between TMS group and sham group	the score change of PRM(pattern recognition memory) score	4 weeks
Secondary	the comparison of change of K-MMSE between TMS group and sham group	the score change of K-MMSE(Korean version of mini mental status exam)	8 weeks
Secondary	the comparison of long term change of K-MoCA between TMS group and sham group	the score change of K-MoCA (Korean version of Montreal cognitive assessment)	8 weeks
Secondary	the comparison of long term change of CDR-SOB between TMS group and sham group	the score change of CDR-SOB(Clinical dementia rating-sum of boxes)	8 weeks
Secondary	the comparison of long term change of ADAS-Cog between TMS group and sham group	the score change of ADAS-Cog ( the Alzheimer's disease assessment scale-cognitive subscale)	8 weeks
Secondary	the comparison of long term change of COWAT score between TMS group and sham group	the score change of COWAT(controlled oral word association) score	8 weeks
Secondary	the comparison of long term change of stroop test score between TMS group and sham group	the score change of stroop test score	8 weeks
Secondary	the comparison of long term change of TMT score between TMS group and sham group	the score change of TMT(trail making test)	8 weeks
Secondary	the comparison of long term change of RVP score between TMS group and sham group	the score change of RVP(raid visual information processing)	8 weeks
Secondary	the comparison of long term change of SWM score between TMS group and sham group	the score change of SWM (spatial working memory) score	8 weeks
Secondary	the comparison of long term change of cognitive function between TMS group and sham group	the score change of PRM(pattern recognition memory) score	8 weeks
Secondary	the comparison of short term change of mood (depression) between TMS group and sham group	the score change of GDS (geriatric depression scale) short form	4 weeks
Secondary	the comparison of long term change of mood (depression) between TMS group and sham group	the score change of GDS (geriatric depression scale) short form	8 weeks
Secondary	the comparison of short term change of ADL between TMS group and sham group	the score change of S-IADL(Seoul instrumental activity of daily life )	4 weeks
Secondary	the comparison of long term change of ADL between TMS group and sham group	the score change of S-IADL(Seoul instrumental activity of daily life )	8 weeks
Secondary	the comparison of change of resting fMRI between TMS group and sham group	the qualititve change of resting fMRI	4 weeks
Secondary	the comparison of change of FA value between TMS group and sham group	the change of FA(fractional anisotropy) value in DTI(diffusion tensor imaging) analysis	4 weeks