Sargramostim for Alzheimer's Disease

(SESAD Trial)

Overseen By Neurology Research, CU Department of Neurology

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Colorado, Denver

Must be taking: Cholinesterase inhibitors, Memantine

Must not be taking: NSAIDs, Anticoagulants

Disqualifiers: Cancer, Seizures, Hepatitis, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

42 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of sargramostim, a medicine typically used for bone marrow issues, to determine if it can aid individuals with mild-to-moderate Alzheimer's disease. Participants will receive either sargramostim or a placebo (a harmless substance resembling the treatment) for six months. Individuals diagnosed with Alzheimer's who experience symptoms like memory loss but can still care for themselves might be suitable candidates. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, providing participants an opportunity to contribute to significant advancements in Alzheimer's treatment.

Will I have to stop taking my current medications?

The trial requires that participants be stable on all medications for at least 30 days before the initial screening visit. If you are receiving anti-dementia treatment, you must be on a stable dose for at least 2 months before the screening.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that sargramostim, also known as Leukine, has been tested for safety in people with Alzheimer's disease. Studies have found it to be generally well-tolerated, meaning most people can use it without problems. Importantly, these trials did not link any serious side effects to the drug. The FDA has already approved sargramostim for other uses, such as aiding bone marrow, which supports its safety profile. This indicates it has been used safely in people before, though not specifically for Alzheimer's until now. So far, the results appear promising for safety in Alzheimer's patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Alzheimer's?

Researchers are excited about Sargramostim for Alzheimer's disease because it works differently from typical treatments like cholinesterase inhibitors or NMDA receptor antagonists. Sargramostim is unique because it is designed to stimulate the immune system by increasing the production of white blood cells, potentially reducing inflammation in the brain, which is a key factor in Alzheimer's progression. Unlike most Alzheimer's treatments that focus on symptom management, Sargramostim aims to target the underlying disease processes, offering hope for not just slowing but possibly altering the course of the disease.

What evidence suggests that sargramostim might be an effective treatment for Alzheimer's disease?

Research has shown that sargramostim, also known as Leukine, offers promising results for people with mild-to-moderate Alzheimer's disease. In previous studies, patients who received sargramostim experienced noticeable improvements in memory and thinking skills. The treatment also affected biomarkers, which indicate the disease's presence or progression. Additionally, patients generally tolerated the drug well, with no serious side effects linked to the treatment. In this trial, participants will receive either sargramostim or a placebo control (saline) to further evaluate its potential to slow down or improve Alzheimer's disease symptoms. ^{1 2 3 4 5}

Who Is on the Research Team?

Huntington Potter, PhD

Principal Investigator

University of Colorado Alzheimer's and Cognition Center

Are You a Good Fit for This Trial?

This trial is for individuals aged 60-80 with mild-to-moderate Alzheimer's Disease, who have a caregiver available and meet specific cognitive criteria. They must not have certain medical conditions or be on treatments that could affect the study results.

Inclusion Criteria

I can see and hear well enough to participate.

Be willing / able to provide written informed consent or assent

My tests show positive signs of brain amyloid, indicating Alzheimer's.

Exclusion Criteria

Is a prisoner

Is unable to read/write at a 6th grade level

I have a history of blood clots in my veins or lungs.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive sargramostim or placebo subcutaneously 5 days per week for 24 weeks

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Saline - placebo comparator
• Sargramostim

Trial Overview The trial tests sargramostim, an FDA-approved drug for bone marrow stimulation, against a saline placebo to assess its safety and effectiveness in treating Alzheimer's over six months.

How Is the Trial Designed?

Group I: Sargramostim Experimental Treatment 1 Intervention

250 mcg/m2/day subcutaneously 5 days/week for 24 weeks

Group II: Placebo Control - Saline Placebo Group 1 Intervention

Placebo comparator (saline) subcutaneously 5days/week for 24 weeks

Sargramostim is already approved in United States, European Union for the following indications:

Approved in United States as Leukine for:

• Bone Marrow Stimulation
• Neutropenia
• Acute Myeloid Leukemia
• Fungal Infections
• Radiation Exposure

Approved in European Union as Leukine for:

• Bone Marrow Stimulation
• Neutropenia
• Acute Myeloid Leukemia

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Alzheimer's Association

Collaborator

Trials

103

Recruited

44,300+

Partner Therapeutics, Inc.

Industry Sponsor

Trials

7

Recruited

820+

Published Research Related to This Trial

In a study of 15 pediatric patients with malignancies and invasive fungal diseases (IFDs), sargramostim showed a high overall response rate of 92%, indicating its potential effectiveness as an adjunctive treatment for patients who are neutropenic and refractory to antifungal therapy.

A systematic review of 65 cases, including the 15 new patients, demonstrated an overall response rate of 82% for sargramostim in treating IFDs, suggesting it may serve as a valuable immunomodulator for patients with hematological malignancies facing difficult-to-treat fungal infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor (rhu GM-CSF) as Adjuvant Therapy for Invasive Fungal Diseases. Chen, TK., Batra, JS., Michalik, DE., et al.[2022]

In a study analyzing 990 patients treated with sargramostim and matched cohorts receiving filgrastim or pegfilgrastim, sargramostim was associated with a 56% lower risk of infection-related hospitalizations for those undergoing chemotherapy-induced neutropenia.

Patients using sargramostim also experienced significantly lower hospitalization costs, with reductions of 84% compared to filgrastim and 62% compared to pegfilgrastim, highlighting its potential economic benefits in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of hospitalization risk and associated costs among patients receiving sargramostim, filgrastim, and pegfilgrastim for chemotherapy-induced neutropenia. Heaney, ML., Toy, EL., Vekeman, F., et al.[2022]

A case report described an adverse reaction to sargramostim (rhu GM-CSF) involving symptoms like itching, hives, and throat tightness, highlighting the potential for allergic reactions to this treatment.

Prick skin testing showed that the patient was sensitized to sargramostim but not to filgrastim (rhu G-CSF), suggesting that skin testing could help identify patients at risk for allergic reactions to GM-CSF therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immediate hypersensitivity to human recombinant granulocyte-macrophage colony-stimulating factor associated with a positive prick skin test reaction. Engler, RJ., Weiss, RB.[2017]

Sargramostim (GM-CSF) significantly improves symptoms and histological outcomes in a mouse model of acute colitis, indicating its potential as a treatment for inflammatory bowel diseases like Crohn's disease.

The therapeutic effects of GM-CSF are linked to its ability to expand plasmacytoid dendritic cells (pDCs) and enhance type 1 interferon production, suggesting a specific immune mechanism that could be targeted for better treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Granulocyte macrophage colony-stimulating factor ameliorates DSS-induced experimental colitis. Sainathan, SK., Hanna, EM., Gong, Q., et al.[2021]

Sargramostim is effective in accelerating hematologic recovery in patients exposed to bone marrow-suppressing agents, leading to fewer infections and improved survival outcomes in various clinical settings.

As an immune modulator, sargramostim enhances anti-cancer responses when used alongside conventional therapies, showing a favorable safety profile and potential for expanded use in treating immune-related conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sargramostim (rhu GM-CSF) as Cancer Therapy (Systematic Review) and An Immunomodulator. A Drug Before Its Time? Lazarus, HM., Ragsdale, CE., Gale, RP., et al.[2022]

A 49-year-old woman receiving sargramostim (GM-CSF) therapy for hepatitis C developed severe neurological symptoms, including confusion and gait disturbance, within two weeks of treatment.

Autopsy revealed diffuse lymphoid infiltrates in the central nervous system, highlighting a potential serious adverse effect of GM-CSF therapy that may become more common as its use increases in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulminant CNS perivascular lymphocytic proliferation: association with sargramostim, a hematopoietic growth factor. Riggs, JE., Mansmann, PT., Cook, LL., et al.[2017]

In a study involving 35 patients (18 receiving GM-CSF and 17 controls), GM-CSF did not enhance T cell or natural killer cell recovery after allogeneic stem cell transplantation, contrary to expectations.

However, GM-CSF administration improved dendritic cell reconstitution in patients undergoing autologous stem cell transplantation, suggesting its benefits may vary based on the type of transplant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Granulocyte-macrophage colony-stimulating factor increases the proportion of circulating dendritic cells after autologous but not after allogeneic hematopoietic stem cell transplantation. Eksioglu, EA., Kielbasa, J., Eisen, S., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7988877/

Safety and efficacy of sargramostim (GM‐CSF) in the ... Results. Sargramostim treatment expectedly changed innate immune system markers, with no drug‐related serious adverse events or amyloid‐related ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT01409915

NCT01409915 | Study of the Safety & Efficacy of Leukine® ... 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 ...

3. partnertx.com partnertx.com/partner-therapeutics-announces-publication-of-clinical-trial-results-showing-significant-benefit-with-use-of-leukine-sargramostim-in-patients-with-alzheimers-disease/

Patients with mild-to-moderate Alzheimer's disease ... Patients with mild-to-moderate Alzheimer's disease (AD) receiving Leukine experienced significant reversal of cognitive loss and biomarkers of disease ...

4. reporter.nih.gov reporter.nih.gov/project-details/10534753

Phase II trial of GM-CSF/sargramostim in Alzheimer's ... We also found that recombinant human GM-CSF(sargramostim/Leukine) treatment is associated with cognitive improvements in leukemia patients after bone marrow ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04902703

Phase II Trial to Evaluate Safety and Efficacy of GM-CSF ... This trial protocol is designed to evaluate primarily whether the long-term use of sargramostim (recombinant human GM-CSF), administered five days per week ...