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

University of Colorado Denver (CU Denver)

Status and phase: Completed; Phase 2

Conditions: Alzheimer's Disease

Treatments: Drug: Sagramostim; Drug: Saline -- placebo comparator

Study type: Interventional

Funder types: Other

Identifiers

NCT01409915

12-1273

Details and patient eligibility

About

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.

Full 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.

Enrollment: 44 patients

Sex: All

Ages: 55 to 85 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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44 participants in 2 patient groups, including a placebo group

Sagramostim (Leukine)

Experimental group

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

Treatment:

Drug: Sagramostim

Control Group

Placebo Comparator group

Description:

Saline -- placebo comparator. Given as a subcutaneous injection.

Treatment:

Drug: Saline -- placebo comparator