Back to resultsStudy of the Safety & Efficacy of Leukine® in the Treatment of Alzheimer's Disease
Primary Purpose
Alzheimer's Disease
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Sagramostim
Saline -- placebo comparator
Sponsored by
About this trial
This is an interventional treatment trial for Alzheimer's Disease focused on measuring Alzheimer's disease, neuropsychological assessment, Granulocyte-Macrophage Colony-Stimulating Factor, Leukine
Eligibility Criteria
Inclusion Criteria:
- age 55 to 85 years;
- should have a mild-to-moderate AD diagnosis (MMSE 10-26 inclusive);
- should have evidence of elevated cortical amyloid by PET using florbetapir F18 (Amyvid) [i.e. a positive scan], assessed qualitatively according to the Amyvid product label.
- if on anti-dementia treatment should be on stable treatment for at least 2 months (i.e. cholinesterase inhibitor and/or Memantine or Axona);
- stable on all other medications for at least 30 days prior to screen;
- should be fluent in English;
- should be physically able to participate by medical history, clinical exam and tests;
- should have a study partner to accompany them to scheduled visits.
Exclusion Criteria:
- clinically relevant arrhythmias;
- a resting pulse less than 50;
- active cancer other than non-melanoma skin cancers;
- use of another investigatory drug within 2 months of screening;
- significant stroke or head trauma by history or MRI;
- contraindication for having a MRI;
- diagnostic and Statistical Manual of Mental Disorders-IV criteria for a current major psychiatric disorder;
- sensitivity to yeast or yeast products;
- impaired kidney function as measured by a Glomerular Filtration Rate less than 60 milliliters/min;
- preexisting fluid retention, pulmonary infiltrates, or congestive heart failure;
- history of moderate-to-severe lung disease;
- history of moderate-to-severe liver disease;
- pregnant women, or any women who feel they are likely to become pregnant during the study;
- prisoners.
Sites / Locations
- University of Colorado Denver, Anschutz Medical Campus
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Sagramostim (Leukine)
Control Group
Arm Description
5 subjects 250 mcg /m2/day Leukine subcutaneously for 5 days/week for three weeks. Data and Safety Monitoring Board will then review data and recommend whether to continue at the same current recommended dose for additional subjects or to reduce the dose by half if excessive leukocytosis occurs
Saline -- placebo comparator. Given as a subcutaneous injection.
Outcomes
Primary Outcome Measures
Adverse Events (AEs) by Body System
Count of AE's from Consent to Follow-up 2 within a safety analysis set consisting of all participants who were enrolled and randomized and who received at least one injection of sargramostim or placebo
Secondary Outcome Measures
MMSE (Mini Mental State Examination) From Baseline to End of Treatment (3 Weeks), Follow-Up 1 (45 Days Post Treatment) and Follow-Up 2 (90 Days Post Treatment)
Mini-Mental State Examination (MMSE) is a brief psychometric instrument developed to assess cognitive function in elderly populations. It is a standard assessment used by all NIH Alzheimer's Disease Centers (ADCCs and ADRCs) to identify and monitor individuals with AD. The range for scores in the MMSE is from 0 to 30, with lower scores indicating greater impairment.
Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13) From Baseline to End of Treatment (3 Weeks), Follow-Up 1 (45 Days Post Treatment) and Follow-Up 2 (90 Days Post Treatment)
Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS-Cog13). The ADAS-Cog13 is the most popular cognitive testing instrument used in clinical trials of nootropics (drugs or agents that improve cognitive function). It consists of 13 tasks measuring the disturbances of memory, language, praxis, attention and other cognitive abilities, which are often referred to as the core symptoms of AD. Score ranges from 0-85, with a higher score representing more severe impairment
Full Information
NCT ID
NCT01409915
First Posted
August 2, 2011
Last Updated
May 12, 2021
Sponsor
University of Colorado, Denver
Collaborators
The Dana Foundation
1. Study Identification
Unique Protocol Identification Number
NCT01409915
Brief Title
Study of the Safety & Efficacy of Leukine® in the Treatment of Alzheimer's Disease
Official Title
Pilot Phase 2 Trial of the Safety & Efficacy of Granulocyte-Macrophage Colony-Stimulating Factor (Leukine®) in the Treatment of Alzheimer's Disease
Study Type
Interventional
2. Study Status
Record Verification Date
May 2021
Overall Recruitment Status
Completed
Study Start Date
March 2011 (undefined)
Primary Completion Date
December 9, 2019 (Actual)
Study Completion Date
December 9, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Colorado, Denver
Collaborators
The Dana Foundation
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
A medicine that is FDA-approved for bone marrow stimulation (called Leukine) will be tested for its ability to be tolerated by Alzheimer's disease patients and potentially to improve their memory.
Detailed Description
Preliminary preclinical results demonstrated that GM-CSF (Granulocyte macrophage colony-stimulating factor, e.g. Leukine®/Sargramostim) rapidly reduced cerebral amyloid deposition and completely reversed memory deficits in transgenic mouse models of Alzheimer's Disease (AD). To assess the efficacy of GM-CSF in humans, the investigators performed a retrospective analysis of a cognition study of human patients undergoing hematopoietic cell transplantation for cancer and who garner cognitive impairments from the chemotherapy or irradiation. In the patients that received a colony-stimulating factor (CSF) to stimulate the bone marrow and recover immune system function, the investigators found that those who received GM-CSF (Leukine®/Sargramostim) plus G-CSF (Filigrastim) significantly improved in cognitive function as compared to those who received G-CSF alone. These findings combined with over two decades of accrued safety data using recombinant human GM-CSF, Leukine®/Sargramostim, in elderly leukopenic patients, suggested that Leukine® should be tested as a treatment to reverse cerebral amyloid pathology and cognitive impairment in AD.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer's Disease
Keywords
Alzheimer's disease, neuropsychological assessment, Granulocyte-Macrophage Colony-Stimulating Factor, Leukine
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
44 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Sagramostim (Leukine)
Arm Type
Experimental
Arm Description
5 subjects 250 mcg /m2/day Leukine subcutaneously for 5 days/week for three weeks. Data and Safety Monitoring Board will then review data and recommend whether to continue at the same current recommended dose for additional subjects or to reduce the dose by half if excessive leukocytosis occurs
Arm Title
Control Group
Arm Type
Placebo Comparator
Arm Description
Saline -- placebo comparator. Given as a subcutaneous injection.
Intervention Type
Drug
Intervention Name(s)
Sagramostim
Other Intervention Name(s)
Leukine, Granulocyte-Macrophage Colony-Stimulating Factor
Intervention Description
5 subjects 250 mcg /m2/day Leukine subcutaneously for 5 days/week for three weeks. Data and Safety Monitoring Board will then review data and recommend whether to continue at the same current recommended dose for additional subjects or to reduce the dose by half if excessive leukocytosis occurs
Intervention Type
Drug
Intervention Name(s)
Saline -- placebo comparator
Other Intervention Name(s)
Sterile solution of sodium chloride in water
Intervention Description
subcutaneous injection
Primary Outcome Measure Information:
Title
Adverse Events (AEs) by Body System
Description
Count of AE's from Consent to Follow-up 2 within a safety analysis set consisting of all participants who were enrolled and randomized and who received at least one injection of sargramostim or placebo
Time Frame
20 weeks (From Consent to Follow-up 2)
Secondary Outcome Measure Information:
Title
MMSE (Mini Mental State Examination) From Baseline to End of Treatment (3 Weeks), Follow-Up 1 (45 Days Post Treatment) and Follow-Up 2 (90 Days Post Treatment)
Description
Mini-Mental State Examination (MMSE) is a brief psychometric instrument developed to assess cognitive function in elderly populations. It is a standard assessment used by all NIH Alzheimer's Disease Centers (ADCCs and ADRCs) to identify and monitor individuals with AD. The range for scores in the MMSE is from 0 to 30, with lower scores indicating greater impairment.
Time Frame
From Baseline to End of Treatment (3 weeks), Follow-Up 1 (45 days post treatment) and Follow-Up 2 (90 days post treatment)
Title
Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13) From Baseline to End of Treatment (3 Weeks), Follow-Up 1 (45 Days Post Treatment) and Follow-Up 2 (90 Days Post Treatment)
Description
Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS-Cog13). The ADAS-Cog13 is the most popular cognitive testing instrument used in clinical trials of nootropics (drugs or agents that improve cognitive function). It consists of 13 tasks measuring the disturbances of memory, language, praxis, attention and other cognitive abilities, which are often referred to as the core symptoms of AD. Score ranges from 0-85, with a higher score representing more severe impairment
Time Frame
Baseline to End of Treatment (3 weeks), Follow-Up 1 (45 days post treatment) and Follow-Up 2 (90 days post treatment)
Other Pre-specified Outcome Measures:
Title
Alzheimer's Disease Cooperative Study -Activities of Daily Living Inventory (ADCS-ADL) From Baseline to End of Treatment (3 Weeks), Follow-Up 1 (45 Days Post Treatment) and Follow-Up 2 (90 Days Post Treatment)
Description
The ADCS-ADL is a caregiver/study partner rated questionnaire of 23 items, with possible scores over a range of 0-78, where 78 implies full functioning with no impairment. The ADCS-ADL assesses functional capacity across a wide spectrum of severity
Time Frame
Baseline to End of Treatment (3 weeks), Follow-Up 1 (45 days post treatment) and Follow-Up 2 (90 days post treatment)
Title
Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) From Baseline to End of Treatment (3 Weeks), Follow-Up 1 (45 Days Post Treatment) and Follow-Up 2 (90 Days Post Treatment)
Description
The CDR is a study partner/caregiver and participant based interview to assess changes in domains such as memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. Each domain is rated as 0 (no dementia), 0.5 (uncertain dementia), 1 (mild dementia), 2 (moderate dementia), or 3 (severe dementia). The Sum of Boxes score (CDR-SB) score was tallied for each administration using the rules from the Washington University Knight ADRD scoring algorithm. Scores range from 0-18. The higher the score, the worse the impairment.
Time Frame
Baseline to End of Treatment (3 weeks), Follow-Up 1 (45 days post treatment) and Follow-Up 2 (90 days post treatment)
Title
Trail Making Test - Part A (TMT-A) From Baseline to End of Treatment (3 Weeks), Follow-Up 1 (45 Days Post Treatment) and Follow-Up 2 (90 Days Post Treatment)
Description
The Trail Making Test- part A (TMT-A) is a assessment of psychomotor speed and is a timed test in which participants must connect a series of numbers randomly placed on a page. Time range is between 0 and 150 seconds, with higher score representing worse performance.
Time Frame
Baseline to End of Treatment (3 weeks), Follow-Up 1 (45 days post treatment) and Follow-Up 2 (90 days post treatment)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
55 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
age 55 to 85 years;
should have a mild-to-moderate AD diagnosis (MMSE 10-26 inclusive);
should have evidence of elevated cortical amyloid by PET using florbetapir F18 (Amyvid) [i.e. a positive scan], assessed qualitatively according to the Amyvid product label.
if on anti-dementia treatment should be on stable treatment for at least 2 months (i.e. cholinesterase inhibitor and/or Memantine or Axona);
stable on all other medications for at least 30 days prior to screen;
should be fluent in English;
should be physically able to participate by medical history, clinical exam and tests;
should have a study partner to accompany them to scheduled visits.
Exclusion Criteria:
clinically relevant arrhythmias;
a resting pulse less than 50;
active cancer other than non-melanoma skin cancers;
use of another investigatory drug within 2 months of screening;
significant stroke or head trauma by history or MRI;
contraindication for having a MRI;
diagnostic and Statistical Manual of Mental Disorders-IV criteria for a current major psychiatric disorder;
sensitivity to yeast or yeast products;
impaired kidney function as measured by a Glomerular Filtration Rate less than 60 milliliters/min;
preexisting fluid retention, pulmonary infiltrates, or congestive heart failure;
history of moderate-to-severe lung disease;
history of moderate-to-severe liver disease;
pregnant women, or any women who feel they are likely to become pregnant during the study;
prisoners.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Huntington Potter, PhD
Organizational Affiliation
University of Colorado, Denver
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Colorado Denver, Anschutz Medical Campus
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Study of the Safety & Efficacy of Leukine® in the Treatment of Alzheimer's Disease
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