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

• ClinicalTrials.gov Identifier: NCT01409915
• Recruitment Status: Completed
• First Posted: August 4, 2011
• Last Update Posted: March 16, 2020
• Sponsor: University of Colorado, Denver
• Collaborator: The Dana Foundation
• Information provided by (Responsible Party): University of Colorado, Denver

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.

Condition or disease	Intervention/treatment	Phase
Alzheimer's Disease	Drug: Sagramostim; Drug: Saline -- placebo comparator	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• 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 Start Date: March 2011
• Actual Primary Completion Date: December 9, 2019
• Actual Study Completion Date: December 9, 2019

Arms and Interventions

Arm	Intervention/treatment
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	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
Placebo Comparator: Control Group; Saline -- placebo comparator. Given as a subcutaneous injection.	Drug: Saline -- placebo comparator; subcutaneous injection; Other Name: Sterile solution of sodium chloride in water

Outcome Measures

Primary Outcome Measures :

1. 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

Secondary Outcome Measures :

1. 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)

Eligibility Criteria

• Ages Eligible for Study: 55 Years to 85 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Colorado

University of Colorado Denver, Anschutz Medical Campus

Aurora, Colorado, United States, 80045

Sponsors and Collaborators

University of Colorado, Denver

The Dana Foundation

Investigators

• Principal Investigator: Huntington Potter, PhD; University of Colorado, Denver

More Information

• Responsible Party: University of Colorado, Denver
• ClinicalTrials.gov Identifier: NCT01409915
• Other Study ID Numbers: 12-1273
• First Posted: August 4, 2011
• Last Update Posted: March 16, 2020
• Last Verified: March 2020

Keywords provided by University of Colorado, Denver:

Alzheimer's disease; neuropsychological assessment; Granulocyte-Macrophage Colony-Stimulating Factor; Leukine

Additional relevant MeSH terms:

Alzheimer Disease; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Molgramostim; Sargramostim; Dementia; Tauopathies; Immunologic Factors; Physiological Effects of Drugs; Antineoplastic Agents