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Study of the Safety & Efficacy of Leukine® in the Treatment of Alzheimer's Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01409915
Recruitment Status : Completed
First Posted : August 4, 2011
Results First Posted : March 23, 2021
Last Update Posted : June 2, 2021
Sponsor:
Collaborator:
The Dana Foundation
Information provided by (Responsible Party):
University of Colorado, Denver

Tracking Information
First Submitted Date  ICMJE August 2, 2011
First Posted Date  ICMJE August 4, 2011
Results First Submitted Date  ICMJE February 25, 2021
Results First Posted Date  ICMJE March 23, 2021
Last Update Posted Date June 2, 2021
Study Start Date  ICMJE March 2011
Actual Primary Completion Date December 9, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 12, 2021)
Adverse Events (AEs) by Body System [ Time Frame: 20 weeks (From Consent to Follow-up 2) ]
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
Original Primary Outcome Measures  ICMJE
 (submitted: August 3, 2011)
Ability of AD subjects to tolerate Leukine treatment will be assessed [ Time Frame: 6 months ]
Various tests of well being and toxicity will be monitored for 6 months after treatment
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 12, 2021)
  • 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) [ 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) ]
    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) [ Time Frame: 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
Original Secondary Outcome Measures  ICMJE
 (submitted: August 3, 2011)
Ability of Leukine treatment to improve cognition of AD subjects [ Time Frame: 6 months ]
Neuropsychological measures will be assessed at various intervals up to 6 months following treatment (or placebo)
Current Other Pre-specified Outcome Measures
 (submitted: May 12, 2021)
  • 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) [ Time Frame: Baseline to End of Treatment (3 weeks), Follow-Up 1 (45 days post treatment) and Follow-Up 2 (90 days post treatment) ]
    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
  • 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) [ Time Frame: Baseline to End of Treatment (3 weeks), Follow-Up 1 (45 days post treatment) and Follow-Up 2 (90 days post treatment) ]
    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.
  • 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) [ Time Frame: Baseline to End of Treatment (3 weeks), Follow-Up 1 (45 days post treatment) and Follow-Up 2 (90 days post treatment) ]
    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.
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of the Safety & Efficacy of Leukine® in the Treatment of Alzheimer's Disease
Official Title  ICMJE Pilot Phase 2 Trial of the Safety & Efficacy of Granulocyte-Macrophage Colony-Stimulating Factor (Leukine®) in the Treatment of Alzheimer's Disease
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Alzheimer's Disease
Intervention  ICMJE
  • Drug: Sagramostim
    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
    Other Names:
    • Leukine
    • Granulocyte-Macrophage Colony-Stimulating Factor
  • Drug: Saline -- placebo comparator
    subcutaneous injection
    Other Name: Sterile solution of sodium chloride in water
Study Arms  ICMJE
  • Experimental: Sagramostim (Leukine)
    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: Drug: Sagramostim
  • Placebo Comparator: Control Group
    Saline -- placebo comparator. Given as a subcutaneous injection.
    Intervention: Drug: Saline -- placebo comparator
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 25, 2021)
44
Original Estimated Enrollment  ICMJE
 (submitted: August 3, 2011)
40
Actual Study Completion Date  ICMJE December 9, 2019
Actual Primary Completion Date December 9, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. age 55 to 85 years;
  2. should have a mild-to-moderate AD diagnosis (MMSE 10-26 inclusive);
  3. 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.
  4. if on anti-dementia treatment should be on stable treatment for at least 2 months (i.e. cholinesterase inhibitor and/or Memantine or Axona);
  5. stable on all other medications for at least 30 days prior to screen;
  6. should be fluent in English;
  7. should be physically able to participate by medical history, clinical exam and tests;
  8. should have a study partner to accompany them to scheduled visits.

Exclusion Criteria:

  1. clinically relevant arrhythmias;
  2. a resting pulse less than 50;
  3. active cancer other than non-melanoma skin cancers;
  4. use of another investigatory drug within 2 months of screening;
  5. significant stroke or head trauma by history or MRI;
  6. contraindication for having a MRI;
  7. diagnostic and Statistical Manual of Mental Disorders-IV criteria for a current major psychiatric disorder;
  8. sensitivity to yeast or yeast products;
  9. impaired kidney function as measured by a Glomerular Filtration Rate less than 60 milliliters/min;
  10. preexisting fluid retention, pulmonary infiltrates, or congestive heart failure;
  11. history of moderate-to-severe lung disease;
  12. history of moderate-to-severe liver disease;
  13. pregnant women, or any women who feel they are likely to become pregnant during the study;
  14. prisoners.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 55 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01409915
Other Study ID Numbers  ICMJE 12-1273
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party University of Colorado, Denver
Original Responsible Party Gloria Mokry, University of South Florida
Current Study Sponsor  ICMJE University of Colorado, Denver
Original Study Sponsor  ICMJE University of South Florida
Collaborators  ICMJE The Dana Foundation
Investigators  ICMJE
Principal Investigator: Huntington Potter, PhD University of Colorado, Denver
PRS Account University of Colorado, Denver
Verification Date May 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP