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

Tracking Information
First Submitted Date ICMJE	August 2, 2011
First Posted Date ICMJE	August 4, 2011
Last Update Posted Date	January 18, 2018
Study Start Date ICMJE	March 2011
Estimated Primary Completion Date	November 2018 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: June 24, 2014)	Ability of Alzheimer's Disease subjects to tolerate Leukine treatment will be assessed [ Time Frame: Up to 5 months ]; Various tests of well being and toxicity will be monitored for 3 months after treatment
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	Complete list of historical versions of study NCT01409915 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: June 24, 2014)	Ability of Leukine treatment to improve cognition of Alzheimer's Disease subjects [ Time Frame: Up to 5 months ]; Neuropsychological measures will be assessed at various intervals up to 3 months following treatment (or placebo)
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 Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	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	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	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	Active, not recruiting
Estimated Enrollment ICMJE; (submitted: August 3, 2011)	40
Original Estimated Enrollment ICMJE	Same as current
Estimated Study Completion Date	November 2018
Estimated Primary Completion Date	November 2018 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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.
Sex/Gender	Sexes Eligible for Study: All
Ages	55 Years to 85 Years (Adult, Senior)
Accepts Healthy Volunteers	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	Not Provided
Responsible Party	University of Colorado, Denver
Study Sponsor ICMJE	University of Colorado, Denver
Collaborators ICMJE	The Dana Foundation
Investigators ICMJE	Principal Investigator: Huntington Potter, PhD University of Colorado, Denver
PRS Account	University of Colorado, Denver
Verification Date	January 2018
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP