The Long-Term Safety and Efficacy Follow-Up Study of Subjects Who Completed the Phase I Clinical Trial of Neurostem®-AD

The Long-Term Safety and Efficacy Follow-up Study of Subjects Who Completed the Phase I Clinical Trial of Neurostem®-AD

The purpose of the study is to determine the long-term safety and exploratory efficacy of NEUROSTEM®-AD, administered via an open brain surgery to subjects with dementia of the Alzheimer's type, who were eligible for and enrolled in the earlier part of the phase I. Aside from the subjects who completed the earlier part of the Phase I, 3 additional subjects with comparable demographics and disease characteristics as the treatment group will be enrolled into a control group, followed-up for 3 months, and compared for various disease progression indicators with the treatment group.

The hypothesis is that NEUROSTEM®-AD is safe and effective in the treatment of dementia of the Alzheimer's type.

Study Overview

• Status: Unknown
• Conditions: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; Dementia; Alzheimer Disease; Tauopathies; Delirium, Dementia, Amnestic, Cognitive Disorders
• Intervention / Treatment: Biological: NEUROSTEM®-AD

Detailed Description

This is a long-term follow up study of the earlier part of the phase I, during which the safe and effective dose(safety) of NEUROSTEM®-AD was determined for implantation into the brains of subjects with Dementia of the Alzheimer's type. Subjects with Dementia of the Alzheimer's type, who signed the informed consent form and meet the eligibility criteria, were implanted with a single dose of NEUROSTEM®-AD, hUBC-MSCs, into the brain. The subjects were hospitalized for 5 to 10 days following the surgical implantation and were observed for acute adverse events: Gradient echo MRI within the the 24 hours post-op, vital signs, clinical laboratory tests, chest x-rays within Day 2. On Day 14, DLT was assessed, and the subjects were followed up on the safety and disease progression of dementia (of the Alzheimer's type) for 12 weeks post-implantation.

In this part of the study, the subjects described above will be followed-up for upto Month 24, and 3 additional subjects with comparable demographics and disease characteristics as the treatment group (refer to Inclusion/Exclusion Criteria) will be enrolled as a control group, followed up for 3 months and compared with the treatment group for various indicators of the disease progression.

• Study Type: Observational
• Enrollment (Anticipated): 14

Contacts and Locations

• Study Contact: Name: Duk-Lyul Na, MD, PhD; Phone Number: +82-2-3410-3594; Email: dukna@naver.com

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 135-710
    • Recruiting
    • Samsung Medical Center
    • Contact: Duk L. Na, MD, PhD; Phone Number: +82-2-3410-3594; Email: dukna@naver.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The patients, who were administered with NEUROSTEM®-AD in the earlier part of the Phase I study, will be compared with the patients, who have similar demographics and disease characteristics as the subjects in the test group but have not been treated with NEUROSTEM®-AD.

Description

TEST GROUP

Inclusion Criteria:

• Subjects who have enrolled and completed the Phase I cliical trial: The Safety and The Efficacy Evaluation of NEUROSTEM®-AD in Patients With Alzheimer's Disease
• Subjects who are willing to participate in the study and sign the consent form

Exclusion Criteria:

• Females who are pregnant or nursing
• Subjects who have participated in another clinical study within the 3 months prior to the initiation of this study
• Subjects who are restricted from undergoing exams perfomed during the study (i.e. MRI, CT, or PET screening)
• Subjects who the principal investigator considers inappropriate for participation in the study due to any reasons other than those listed above

CONTROL GROUP

Inclusion Criteria:

• Patients with a moderate alzheimer's disease, diagnosed with a dementia of alzheimer's type, according to the DSM-VI and NINCDS-ADRDA criteria, and shows amyloid-positive in a PIB-PET

Exclusion Criteria:

• Subjects with a psychological disease (i.e. depression, schizophrenia, bipolar disorder, etc)
• Subjects with a dementia caused by other degenerative neurological diseases (infection of the CNS, such as HIV or Syphilis), head trauma, Creutzfeld-Jacob disease, Pick's disease, Huntington's disease, and Parkinson's disease)
• Subjects with a vascular dementia as determined by the clinical criteria of DSM IV and the imaging criteria of Erkinjuntii
• Subjects with severe white matter hyperintensities (WMH); Severe WMH is defined as, according to Clinical Research Center for Dementia of South Korea, a condition in which the deep white matter is 25 mm or greater and the periventricular capping/banding is 10 mm or greater in lengths.
• Subjects with a history of stroke within the 3 months prior to the study enrollment
• Subjects with a severe liver disease (ALT/AST values are higher than twice the normal range)
• Subjects with a severe renal disease (1.5mg/dL or more of serum creatinine)
• Pregnant or lactating women
• Subjects with abnormal findings of the clinical laboratory values at Visit 1:
• Hemoglobin < 9.5g/dL in male < 9.0 g/dL in female
• Total WBC count < 3000/mm3
• Total bilirubin ≥ 3 mg/dL
• Subjects with a suspected active lung disease, based on the chest X-ray result at Visit 1
• Females of childbearing age who does not practice medically acceptable method of contraception during the study
• Subjects who have previously failed Screening for participation in this study
• Subjects who have participated in another clinical study within the 3 months prior to the initiation of this study
• Subjects with a bleeding disorder (platelet count < 150,000/mm3; PT ≥ 1.5; INR or aPTT ≥ 1.5 X control
• Subjects with a cancer (including brain tumor)
• Subjects with a history of alcohol or drug abuse
• Subjects who are restricted from undergoing exams perfomed during the study (i.e. MRI, CT, or PET screening)
• Patients who the principal investigator considers inappropriate for participation in the study due to any reasons other than those listed above

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
NEUROSTEM®-AD; A single administration of human umbilical cord blood-derived mesenchymal stem cells through a brain surgery DOSE A - 250,000 cells per entry site, 3 million cells per brain; DOSE B - 500,000 cells per entry site, 6 million cells per brain	Biological: NEUROSTEM®-AD; NEUROSTEM®-AD was administered to eligible subjects in the early part of the Phase I clinical study. In this follow-up study, no intervention will be performed.; Other Names: human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs)
Control Group; A group of subjects with comparable demographics (age and gender) and disease characteristics [Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB)] as the NEUROSTEM®-AD-treated group, but did not receive the treatment with NEUROSTEM®-AD and were continued on conventional therapy. Restrictions in the concurrent use of drug therapy are as follows: Patients are, in principle, permitted to continue the drug therapy they were on prior to the enrollment, for the treatment of concurrent illnesses other than Dementia, such as hypertension, diabetes mellitus, or hyperlipidemia. For drugs used in the treatment of dementia, behavior-modifying drugs can be added to the pharmacological regimen of a subject during the course of the study. However, adding a new cognitive enhancer, such as donepezil, memantine, galantamine, rivastigmine, is not permitted while dose adjustment is permitted given that the drug had been in use prior to the initiation of the study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety	Incidence rate ot adverse events (vital signs, physical examination, mixed lymphocyte reaction, and laboratory tests)	upto 24 months post-op

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy	Primary Efficacy Variable: ADAS-cog response rate, ADAS-cog response is defined as when ADAS-cog score at the end of the study is not worse than the Baseline score. Secondary Efficacy Variables: Changes in Seoul Instrumental Activities of Daily Living (S-IADL); Changes in Mini Mental State Examination Korean verson (K-MMSE); Changes in Caregiver-administered Neuropsuchiatric Inventory; Changes in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog); Changes in CMRglc: regional cerebral metabolic rate for glucose (FDG-PET)	upto 24 months post-op

Collaborators and Investigators

• Sponsor: Duk Lyul Na
• Collaborators: Medipost Co Ltd.
• Investigators: Principal Investigator: Duk L. Na, MD,PhD, Samsung Medical Center

Publications and helpful links

General Publications

• Kim HJ, Seo SW, Chang JW, Lee JI, Kim CH, Chin J, Choi SJ, Kwon H, Yun HJ, Lee JM, Kim ST, Choe YS, Lee KH, Na DL. Stereotactic brain injection of human umbilical cord blood mesenchymal stem cells in patients with Alzheimer's disease dementia: A phase 1 clinical trial. Alzheimers Dement (N Y). 2015 Jul 26;1(2):95-102. doi: 10.1016/j.trci.2015.06.007. eCollection 2015 Sep.

Helpful Links

• The Safety and The Efficacy Evaluation of NEUROSTEM®-AD in Patients With Alzheimer's Disease

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (Anticipated): September 1, 2013
• Study Completion (Anticipated): September 1, 2013

Study Registration Dates

• First Submitted: September 7, 2012
• First Submitted That Met QC Criteria: September 27, 2012
• First Posted (Estimate): October 1, 2012

Study Record Updates

• Last Update Posted (Estimate): October 1, 2012
• Last Update Submitted That Met QC Criteria: September 27, 2012
• Last Verified: September 1, 2012

More Information

Terms related to this study

• Keywords: Alzheimer, Mesenchymal Stem Cells, Umbilical Cord Blood
• Additional Relevant MeSH Terms: Pathologic Processes; Disease; Mental Disorders; Dementia; Nervous System Diseases; Alzheimer Disease; Brain Diseases; Neurodegenerative Diseases; Cognition Disorders; Central Nervous System Diseases; Neurocognitive Disorders; Tauopathies
• Other Study ID Numbers: MP-CR-007-F/U