Alzheimer's DiseasePhase 2NCT01409915
Study of the Safety & Efficacy of Leukine® in the Treatment of Alzheimer's Disease
A Phase 2 study testing Sagramostim in people with Alzheimer's Disease, run by University of Colorado, Denver at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 55 to 85 years
- Conditions the study is for
- Alzheimer's Disease
- What is being tested?
- Sagramostim
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 44 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2011to 9 Dec 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 55 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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;
Show all 14Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Colorado Denver, Anschutz Medical Campus
Aurora, Colorado, 80045
About this study
Official title: Pilot Phase 2 Trial of the Safety & Efficacy of Granulocyte-Macrophage Colony-Stimulating Factor (Leukine®) in the Treatment of Alzheimer's Disease
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.
Read the 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
- Being tested
- Sagramostim, Saline -- placebo comparator
- Keywords
- Alzheimer's disease, neuropsychological assessment, Granulocyte-Macrophage Colony-Stimulating Factor, Leukine
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SagramostimDrug
Also called Leukine, Granulocyte-Macrophage Colony-Stimulating Factor
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
Saline -- placebo comparatorDrug
Also called Sterile solution of sodium chloride in water
subcutaneous injection
| Study group | Role | What they receive |
|---|---|---|
| Sagramostim (Leukine) | Experimental | 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 Receives: Drug: Sagramostim |
| Control Group | Placebo comparator | Saline -- placebo comparator. Given as a subcutaneous injection. Receives: Drug: Saline -- placebo comparator |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse Events (AEs) by Body System
Count of AE's from Consent to Follow-up 2 within a safety analysis set consisting of all participants who were enrolled and randomized and who received at least one injection of sargramostim or placebo
Measured: 20 weeks (From Consent to Follow-up 2)
Secondary outcomes (2)
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)
Mini-Mental State Examination (MMSE) is a brief psychometric instrument developed to assess cognitive function in elderly populations. It is a standard assessment used by all NIH Alzheimer's Disease Centers (ADCCs and ADRCs) to identify and monitor individuals with AD. The range for scores in the MMSE is from 0 to 30, with lower scores indicating greater impairment.
Measured: From Baseline to End of Treatment (3 weeks), Follow-Up 1 (45 days post treatment) and Follow-Up 2 (90 days post treatment)
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)
Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS-Cog13). The ADAS-Cog13 is the most popular cognitive testing instrument used in clinical trials of nootropics (drugs or agents that improve cognitive function). It consists of 13 tasks measuring the disturbances of memory, language, praxis, attention and other cognitive abilities, which are often referred to as the core symptoms of AD. Score ranges from 0-85, with a higher score representing more severe impairment
Measured: Baseline to End of Treatment (3 weeks), Follow-Up 1 (45 days post treatment) and Follow-Up 2 (90 days post treatment)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Aug 2011 (estimated)
- Study startMar 2011
- Primary completion9 Dec 2019
- Study completion9 Dec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Alzheimer's DiseaseStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Collaborators
- The Dana Foundation
- Responsible party
- Sponsor
- Investigators
- Huntington Potter, PhD, Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01409915
- Sponsor's protocol ID
- 12-1273
- Status last verified
- May 2021
- First submitted
- 2 Aug 2011
- Last updated
- 2 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 2 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Phase 2 Trial of the Safety & Efficacy of Granulocyte-Macrophage Colony-Stimulating Factor (Leukine®) in the Treatment of Alzheimer's Disease
- ClinicalTrials.gov ID
- NCT01409915
- Acronym / sponsor ID
- 12-1273
- Conditions
- Alzheimer's Disease
- Keywords
- Alzheimer's disease, neuropsychological assessment, Granulocyte-Macrophage Colony-Stimulating Factor, Leukine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Collaborators
- The Dana Foundation
- Study start
- Mar 2011
- Primary completion
- 9 Dec 2019 (actual)
- Study completion
- 9 Dec 2019 (actual)
- First posted
- 4 Aug 2011 (estimated)
- Results
- Posted 23 Mar 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sagramostim (Leukine) | Experimental | Drug: Sagramostim5 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 | Placebo comparator | Drug: Saline -- placebo comparatorSaline -- placebo comparator. Given as a subcutaneous injection. |
Who may qualify
- Ages
- 55 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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;
Key exclusion criteria (14 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SagramostimAlso: Leukine, Granulocyte-Macrophage Colony-Stimulating Factor5 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 (Leukine) |
| Saline -- placebo comparatorAlso: Sterile solution of sodium chloride in watersubcutaneous injection | Drug | Control Group |
Primary outcome
Adverse Events (AEs) by Body System
Time frame: 20 weeks (From Consent to Follow-up 2)
Count of AE's from Consent to Follow-up 2 within a safety analysis set consisting of all participants who were enrolled and randomized and who received at least one injection of sargramostim or placebo
2 secondary outcomes
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)
Time frame: From Baseline to End of Treatment (3 weeks), Follow-Up 1 (45 days post treatment) and Follow-Up 2 (90 days post treatment)
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)
Time frame: Baseline to End of Treatment (3 weeks), Follow-Up 1 (45 days post treatment) and Follow-Up 2 (90 days post treatment)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jun 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Huntington Potter, PhD principal investigator
University of Colorado, Denver
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sagramostim in people with Alzheimer's Disease, run by University of Colorado, Denver at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Mar 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adverse Events (AEs) by Body System (time frame: 20 weeks (From Consent to Follow-up 2)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jun 2021.