Clinical trial NCT01409915: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Alzheimer's Disease
Keywords: Alzheimer's disease
neuropsychological assessment
Granulocyte-Macrophage Colony-Stimulating Factor
Leukine
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
Collaborators: name: The Dana Foundation
First posted: 2011-08-04
Enrollment: 44
Sex: ALL
Minimum age (years): 55
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Adverse Events (AEs) by Body System
timeFrame: 20 weeks (From Consent to Follow-up 2)
Secondary outcomes:
measure: 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)
timeFrame: From Baseline to End of Treatment (3 weeks), Follow-Up 1 (45 days post treatment) and Follow-Up 2 (90 days post treatment)
measure: 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)
timeFrame: Baseline to End of Treatment (3 weeks), Follow-Up 1 (45 days post treatment) and Follow-Up 2 (90 days post treatment)
Other outcomes:
measure: 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)
timeFrame: Baseline to End of Treatment (3 weeks), Follow-Up 1 (45 days post treatment) and Follow-Up 2 (90 days post treatment)
measure: 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)
timeFrame: Baseline to End of Treatment (3 weeks), Follow-Up 1 (45 days post treatment) and Follow-Up 2 (90 days post treatment)
measure: 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)
timeFrame: Baseline to End of Treatment (3 weeks), Follow-Up 1 (45 days post treatment) and Follow-Up 2 (90 days post treatment)
Locations:
city: Aurora
country: United States
facility: University of Colorado Denver, Anschutz Medical Campus
state: Colorado
Study officials:
affiliation: University of Colorado, Denver
name: Huntington Potter, PhD
role: PRINCIPAL_INVESTIGATOR
References: