Renew NCP-5 for the Treatment of Mild Cognitive Impairment Due to Alzheimer's Disease (AD) or Mild Dementia of the Alzheimer's Type
Condition: Alzheimer Disease; Cognitive Dysfunction; Mild Cognitive Impairment; Mild Dementia; Cognitive Decline; Dementia, Alzheimer Type
MeSH terms: Alzheimer Disease; Dementia; Cognitive Dysfunction
Intervention: Renew NCP-5
Intervention description: Treatment will be given 3-5 times a week for a total of 35 treatments over 12 weeks.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Participants will be randomized to either the treatment group or the sham group.
Masking: Double (Participant, Outcomes Assessor)
Enrollment: 190.0
Sex: All
Minimum age: 55 Years
Maximum age: 85 Years
Healthy volunteers: No

Summary:

      A Randomized Pivotal Study of RenewTM NCP-5 for the Treatment of Mild Cognitive Impairment
      due to Alzheimer's Disease or Mild Dementia of the Alzheimer's Type is a pivotal, single
      blind, parallel design, multi-site study intends to examine the efficacy and safety of
      RenewTM NCP-5 therapy in the treatment of Cognitive Impairment due to Alzheimer's Disease or
      Mild Dementia of the Alzheimer's Type. Subjects will be prospectively randomized to treatment
      or sham (in a 1:1 ratio) using stratification for Cognitive Impairment due to Alzheimer's
      Disease or Mild Dementia of the Alzheimer's Type, and Cardiovascular Risk (CVR) score at
      multiple sites. Subjects, ages 55-85, will be consented for 13 months and will receive
      thirty-five 60-minute RenewTM NCP-5 treatment sessions during a 7-to-12-week initial
      treatment period, and then transition to a lower frequency maintenance period (twice a week)
      for a total treatment period of 24 weeks.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Be 55-85 years of age at the time of signing the informed consent

          2. Be able to provide consent or have legally authorized representative/caregiver who can
             provide consent

          3. Be able to read and write in English or Spanish

          4. Have a clinical diagnosis consistent with 2011 National Institute of Aging -
             Alzheimer's Association (NIA-AA) "core clinical criteria" guidelines for: (i) The
             diagnosis of dementia due to Alzheimer's disease or (ii) The diagnosis of mild
             cognitive impairment due to Alzheimer's disease:

               -  Montreal Cognitive Assessment (MOCA) score of greater than or equal to 11

               -  All required checkboxes within the study checklist for "The diagnosis of probable
                  AD dementia" must be "yes" or

               -  All required checkboxes within the study checklist for "The diagnosis of mild
                  cognitive impairment due to Alzheimer's disease" must be "yes"

          5. Stable medications for past 30 days and plan to remain on stable medications for the
             first 24 weeks of study participation for treatment of chronic conditions.

          6. Subject should have a caregiver, study partner or companion (which can be a domestic
             party) and may conduct the assessment over the phone if they don't accompany the
             participant).

          7. Must have the potential to improve by at least 2 points or more in the Vascular
             Dementia Assessment Scale cognitive subscale (vADAS-COG)

        Exclusion Criteria:

          1. Unwilling or unable to participate in study procedures

          2. Weight >297 lbs. or >135 kg at screening

          3. Major confounding neurodegenerative or psychiatric disorder unrelated to the condition
             under study, including:

               1. History of clinically-evident stroke

               2. Current uncontrolled epileptic seizures or epilepsy

               3. Multiple Sclerosis or Parkinson's Disease

               4. Current clinically significant major psychiatric disorder (e.g., Major Depressive
                  Disorder) according to the Fifth Edition of Diagnostic and Statistical Manual of
                  Mental Disorders (DSM-V) criteria or significant psychiatric symptoms (e.g.,
                  hallucinations) that could impair the completion of the study

          4. Anyone with active or history of cerebral hemorrhage including subdural & subarachnoid
             or cerebral aneurysm

          5. Evidence of any of the following (based on Section 4.1.1(D) of the 2011 NIA-AA
             guidelines on The diagnosis of dementia due to Alzheimer's disease):

               1. Substantial concomitant cerebrovascular disease, defined by a history of a stroke
                  temporally related to the onset or worsening of cognitive impairment; or the
                  presence of multiple or extensive infarcts or severe white matter hyperintensity
                  burden

               2. Core features of Dementia with Lewy bodies other than dementia itself

               3. Prominent features of behavioral variant frontotemporal dementia

               4. Prominent features of semantic variant primary progressive aphasia or
                  nonfluent/agrammatic variant primary progressive aphasia

               5. Evidence for another concurrent, active neurological disease, non-neurological
                  medical comorbidity or use of medication that could have a substantial effect on
                  cognition

          6. In the opinion of the investigator, any current clinically-significant systemic
             illness or medical condition that is likely to result in deterioration of the
             subject's condition, affect the subject's safety during the study, or to be
             incompatible with performance of the study procedures, including:

               1. History of head trauma with a diagnosis of moderate to severe traumatic brain
                  injury

               2. Known current substantially elevated intracranial pressure

               3. Known current significant sleep deprivation

               4. Known history (within five years) or current significant drug abuse or alcoholism

          7. Any contraindication for MRI such as insulin pumps or pacemakers, including dual
             chamber pacemakers where atrial pacing may interfere with RenewTM NCP-5 inflation
             timing sequence

          8. Hypotension as defined as <80/50 blood pressure at the time of screening

          9. Ongoing uncontrolled severe hypertension (≥ 180 mmHg systolic or ≥ 110 mmHg diastolic

         10. Heart rates < 35 or >125 beats per minute (BPM) at screening

         11. Current uncontrolled arrhythmia. Controlled arrhythmia should have beat-to-beat,
             cycle-length variability less than ±25% at rest.

         12. Current congestive heart failure

         13. Cardiac catheterization within two weeks, any surgical intervention within six weeks
             before RenewTM NCP-5 treatment or a hip or knee replacement within 3 months as long as
             rehab is complete and symptoms have resolved.

         14. Known presence of abdominal aortic aneurysm

         15. Existing aortic insufficiency grade II or higher (regurgitation can prevent diastolic
             augmentation)

         16. Current or past venous thrombosis or thromboembolism

         17. Current limiting peripheral vascular disease with history strongly suggestive of lower
             extremity ischemia or claudication, arterial occlusive disease (aortoiliac,
             ileofemoral, or femoral popliteal)

         18. Demonstrable deficiency in sensation in lower extremities as a result of diabetes or
             other medical condition

         19. Current bleeding disorders.

         20. Current use of major anti-coagulation therapy (such as Heparin therapy or Coumadin®
             therapy) with International Normalized Ratio (INR) > 1.5

         21. Current severe pulmonary disease that prevents the subject from lying supine

         22. Presence of local infection, vasculitis, burn, open wound, or bone fracture on any
             limb which would prevent the ability to perform the RenewTM NCP-5 treatment

         23. Current use of medications that in the investigator's judgement are incompatible with
             the study goals

         24. Significant changes in existing medical plans for treatment of cognitive impairment or
             dementia in last three months and/or or planned changes during the trial

         25. Presence of any of the contraindications for using the RenewTM NCP-5 device

         26. Athletic injuries, including Charley horses, pulled muscles and/or edematous muscles;
             necrotizing cellulitis in the past 30 days which would prevent the ability to perform
             the RenewTM NCP-5 treatment (evaluate and treat prior to RenewTM NCP-5 treatment)

         27. Unwilling or unable to maintain stable exercise regimen throughout the trial

         28. Participation in any clinical drug trial 30 days or five half-lives, whichever is
             longer, prior to screening visit

         29. Use of any device to increase cerebral blood flow in the past 30 days.

         30. History of claustrophobia.

         31. Subject unable to lay supine for 90 minutes