Transcranial Pulse Stimulation (TPS) for Alzheimer's Disease (AD)

Study Overview
=================
Brief Summary
-----------------
This is a prospective open comprehensive proof-of-principle pilot study.

Detailed Description
-----------------
This is a prospective open comprehensive proof-of-principle pilot study with patients of mild to moderate Alzheimer's Disease who have been treated with transcranial pulse stimulation (TPS)

Official Title
-----------------
Transcranial Pulse Stimulation for Alzheimer's Disease in an Open Prospective Pilot Study

Conditions
-----------------
Alzheimer Disease

Intervention / Treatment
-----------------
* Device: NEUROLITH


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Clinically stable patients with probable Alzheimer's Disease (Diagnosis according to ICD-10 Criteria (F00)) MMSE ≥ 10: Mild and moderate Alzheimer's Disease according to AWMF Register, S3 Guidelines of DGN 038/013 and DEGAM 035/021 At least 3 months of stable antidementia therapy or no antidementia therapy necessary (Patients need to continue their standard treatment within the clinical investigation according to the guidelines as TPS is considered an additional treatment to standard therapy) Signed written informed consent 18 years ≤ Age ≤ 85 years Monthly pregnancy tests for female patients in childbearing age Exclusion Criteria: Non-compliance with the protocol (including CERAD-plus) Pregnancy Breast-feeding women Microbubbles (contrast agents) in application area Cerebral pathology unrelated to Alzheimer's disease Metallic objects in the head Neurosurgical intervention of the brain / Craniotomy Cardiac disorders History of psychiatric diseases before development of dementia Hemophilia or other blood clotting disorders Cortisone treatment up to 6 months before first treatment Other conditions implying increased risk according to the judgement of the investigator

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AD Patients<br>All patients were treated with the TPS device (new name: NEUROLITH (Storz Medical AG)) - 6 sessions within 2 weeks, each sessions consisting of 6000 TPS pulses of 0.2 mJ/mm² | Device: NEUROLITH<br>* transcranial pulse stimulation (TPS)<br>* Other names: transcranial pulse stimulation (TPS);|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Consortium to Establish a Registry for Alzheimer's Disease (CERAD) - Total Score | CERAD is a cognitive test battery which is normalized for age, gender and education. The CERAD total score ranges from 0 to 100 with 100 meaning normal cognitive ability and 0 meaning severe cognitive impairment. | 3 months after treatment | 
| Adverse Device Effects | Number of ADEs | within 3 months follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Consortium to Establish a Registry for Alzheimer's Disease (CERAD) - Total Score | CERAD is a cognitive test battery which is normalized for age, gender and education. The CERAD total score ranges from 0 to 100 with 100 meaning normal cognitive ability and 0 meaning severe cognitive impairment. | Immediately post treatment (at 2 weeks) | 
| Consortium to Establish a Registry for Alzheimer's Disease (CERAD) - Total Score | CERAD is a cognitive test battery which is normalized for age, gender and education. The CERAD total score ranges from 0 to 100 with 100 meaning normal cognitive ability and 0 meaning severe cognitive impairment. | 1 month after treatment (at 6 weeks) | 
| Mini-Mental-State Examination (MMSE) | The MMSE consists of 10 items that cover orientation, short term memory, attentional capabilities, arithmetic performance and language functions. Scoring is possible between 0 (worst) and 30 (best). | Immediately post treatment (at 2 weeks) | 
| Mini-Mental-State Examination (MMSE) | The MMSE consists of 10 items that cover orientation, short term memory, attentional capabilities, arithmetic performance and language functions. Scoring is possible between 0 (worst) and 30 (best). | 1 month after treatment (at 6 weeks) | 
| Mini-Mental-State Examination (MMSE) | The MMSE consists of 10 items that cover orientation, short term memory, attentional capabilities, arithmetic performance and language functions. Scoring is possible between 0 (worst) and 30 (best). | 3 months after treatment (at 14 weeks) | 
| Clock Drawing Test (CDT) | The clock drawing test is used to assess visuoconstruction abilities. The subject is asked to draw the face of a clock with all numbers and to set the hands for a specified time (hh:mm). Scores range from 0 (worst) to 7 (best). | Immediately post treatment (at 2 weeks) | 
| Clock Drawing Test (CDT) | The clock drawing test is used to assess visuoconstruction abilities. The subject is asked to draw the face of a clock with all numbers and to set the hands for a specified time (hh:mm). Scores range from 0 (worst) to 7 (best). | 1 month after treatment (at 6 weeks) | 
| Clock Drawing Test (CDT) | The clock drawing test is used to assess visuoconstruction abilities. The subject is asked to draw the face of a clock with all numbers and to set the hands for a specified time (hh:mm). Scores range from 0 (worst) to 7 (best). | 3 months after treatment (at 14 weeks) | 
| Beck Depression Inventory (BDI) | The BDI measures the severity of depression. It is a 21-item questionnaire for self-evaluation with 0-3 scores per item. The total score is the sum of all items. It ranges from 0 (normal state) to 63 (severe depression). | Immediately post treatment (at 2 weeks) | 
| Beck Depression Inventory (BDI) | The BDI measures the severity of depression. It is a 21-item questionnaire for self-evaluation with 0-3 scores per item. The total score is the sum of all items. It ranges from 0 (normal state) to 63 (severe depression). | 1 month after treatment (at 6 weeks) | 
| Beck Depression Inventory (BDI) | The BDI measures the severity of depression. It is a 21-item questionnaire for self-evaluation with 0-3 scores per item. The total score is the sum of all items. It ranges from 0 (normal state) to 63 (severe depression). | 3 months after treatment (at 14 weeks) | 
| Geriatric Depression Scale - short form (GDS-15) | The Geriatric Depression Scale (GDS) is a questionnaire to assess depression in the elderly population. This scale generates self-evaluation scores concerning various aspects with relevance for the depressive disease (e.g. mood, drive, anxiety). The short form contains 15 items. The GDS-15 score ranges from 0 (normal state) to 15 (severe depression). | Immediately post treatment (at 2 weeks) | 
| Geriatric Depression Scale - short form (GDS-15) | The Geriatric Depression Scale (GDS) is a questionnaire to assess depression in the elderly population. This scale generates self-evaluation scores concerning various aspects with relevance for the depressive disease (e.g. mood, drive, anxiety). The short form contains 15 items. The GDS-15 score ranges from 0 (normal state) to 15 (severe depression). | 1 month after treatment (at 6 weeks) | 
| Geriatric Depression Scale - short form (GDS-15) | The Geriatric Depression Scale (GDS) is a questionnaire to assess depression in the elderly population. This scale generates self-evaluation scores concerning various aspects with relevance for the depressive disease (e.g. mood, drive, anxiety). The short form contains 15 items. The GDS-15 score ranges from 0 (normal state) to 15 (severe depression). | 3 months after treatment (at 14 weeks) |