Renew NCP-5 for the Treatment of Mild Cognitive Impairment Due to Alzheimer's Disease (AD) or Mild Dementia of the Alzheimer's Type

Phase 3

Completed

Conditions: Mild Cognitive Impairment
Alzheimer Disease
Cognitive Dysfunction
Mild Dementia
Cognitive Decline
Dementia, Alzheimer Type

Interventions: Device: Renew NCP-5

Registration Number: NCT03721705

Lead Sponsor: Renew Research, LLC

Brief 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 190

Inclusion Criteria

Be 55-85 years of age at the time of signing the informed consent
Be able to provide consent or have legally authorized representative/caregiver who can provide consent
Be able to read and write in English or Spanish
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"
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.
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).
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

Unwilling or unable to participate in study procedures
Weight >297 lbs. or >135 kg at screening
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
Anyone with active or history of cerebral hemorrhage including subdural & subarachnoid or cerebral aneurysm
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
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
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
Hypotension as defined as <80/50 blood pressure at the time of screening
Ongoing uncontrolled severe hypertension (≥ 180 mmHg systolic or ≥ 110 mmHg diastolic
Heart rates < 35 or >125 beats per minute (BPM) at screening
Current uncontrolled arrhythmia. Controlled arrhythmia should have beat-to-beat, cycle-length variability less than ±25% at rest.
Current congestive heart failure
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.
Known presence of abdominal aortic aneurysm
Existing aortic insufficiency grade II or higher (regurgitation can prevent diastolic augmentation)
Current or past venous thrombosis or thromboembolism
Current limiting peripheral vascular disease with history strongly suggestive of lower extremity ischemia or claudication, arterial occlusive disease (aortoiliac, ileofemoral, or femoral popliteal)
Demonstrable deficiency in sensation in lower extremities as a result of diabetes or other medical condition
Current bleeding disorders.
Current use of major anti-coagulation therapy (such as Heparin therapy or Coumadin® therapy) with International Normalized Ratio (INR) > 1.5
Current severe pulmonary disease that prevents the subject from lying supine
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
Current use of medications that in the investigator's judgement are incompatible with the study goals
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
Presence of any of the contraindications for using the RenewTM NCP-5 device
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)
Unwilling or unable to maintain stable exercise regimen throughout the trial
Participation in any clinical drug trial 30 days or five half-lives, whichever is longer, prior to screening visit
Use of any device to increase cerebral blood flow in the past 30 days.
History of claustrophobia.
Subject unable to lay supine for 90 minutes

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Treatment Arm	Renew NCP-5	The first four sessions will be the escalation phase using the Renew NCP-5. There will be a 5-minute ramp up period where the pressure is increased 1 psi/min until the desired pressure is reached. The goal for the treatment group will be at least 2.5 psi for the first treatment, and then escalate the pressure gradually through the fourth session with an average goal of 3 psi/session. After the fourth session, the pressure will be slowly increased to reach the maximum level the subject can tolerate with a goal of reaching 3-6 psi.
Sham Arm	Renew NCP-5	The subjects will receive the same initial and maintenance treatment regimen on the Renew NCP-5. The pressure will not exceed an average of 0.5 psi over all treatments.

Primary Outcome Measures

Name	Time	Method
Mean Change From Baseline to 24 Weeks in Vascular Dementia Assessment Scale Cognitive Subscale (vADAS-cog) Using the Average of Scores at 12, 18 and 24 Weeks.	24 weeks	The vADAS-cog assessment includes 17 subscale scores. The total score is the sum of all scaled scored from 0-120. The higher values represent more cognitive impairment. The change in vADAS-cog scores from baseline at the timepoints of 12, 18, and 24 weeks is averaged together for each patient. The primary outcome measure is the average of those values for all patients in a group.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Treatment Related Adverse Events as Assessed by MedDRA.	24 weeks
Number of Participants With Treatment Related Serious Adverse Events as Assessed by MedDRA.	24 weeks

Trial Locations

Locations (12): Irvine Clinical Research
🇺🇸
Irvine, California, United States
Charter Research
🇺🇸
Lady Lake, Florida, United States
iResearch Savannah
🇺🇸
Savannah, Georgia, United States
Cardiovascular Advantages, LLC
🇺🇸
Baton Rouge, Louisiana, United States
Neuro-Behavioral Clinical Research
🇺🇸
Canton, Ohio, United States
Northwest Clinical Research Center
🇺🇸
Bellevue, Washington, United States
St. James's Hospital
🇮🇪
Dublin, Ireland
Miami Dade Medical Research Institute
🇺🇸
Miami, Florida, United States
iResearch Atlanta
🇺🇸
Atlanta, Georgia, United States
Xenoscience
🇺🇸
Phoenix, Arizona, United States
National University Hospital
🇸🇬
Singapore, Singapore
University of Kansas Medical Center
🇺🇸
Kansas City, Kansas, United States