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

NCT ID: NCT01409915

Last Updated: 2021-06-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-03-31
• Study Completion Date: 2019-12-09

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.

Conditions

Alzheimer's Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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

Group Type: EXPERIMENTAL

Sagramostim

Intervention Type: DRUG

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

Control Group

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

Group Type: PLACEBO_COMPARATOR

Saline -- placebo comparator

Intervention Type: DRUG

subcutaneous injection

Interventions

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

Intervention Type: DRUG

Saline -- placebo comparator

subcutaneous injection

Intervention Type: DRUG

Other Intervention Names

Leukine; Granulocyte-Macrophage Colony-Stimulating Factor; Sterile solution of sodium chloride in water

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.

• Minimum Eligible Age: 55 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Dana Foundation

OTHER

Sponsor Role: collaborator

University of Colorado, Denver

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Huntington Potter, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Colorado, Denver

Locations

University of Colorado Denver, Anschutz Medical Campus

Aurora, Colorado, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

12-1273

Identifier Type: -

Identifier Source: org_study_id