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

Trial Summary

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.

What data supports the effectiveness of the drug Sargramostim for Alzheimer's Disease?

Sargramostim has been shown to boost the immune system and help with recovery after chemotherapy, and it is used in cancer therapy to modulate the immune response. However, its specific effectiveness for Alzheimer's Disease is not well-documented in the provided research. ^{1 2 3 4 5}

Is Sargramostim generally safe for humans?

Sargramostim has been used to help recover bone marrow after chemotherapy and has been approved by the FDA since 1991. However, some people have experienced allergic reactions and other serious side effects, such as confusion and movement problems, which suggests that while it is generally safe, there are potential risks. ^{1 2 3 4 5}

How is the drug Sargramostim unique for treating Alzheimer's disease?

Sargramostim is unique because it is a granulocyte-macrophage colony-stimulating factor (GM-CSF) that activates a broader range of immune cells compared to other treatments, potentially offering a novel approach to modulating the immune system in Alzheimer's disease. ^{1 4 5 6 7}

What is the purpose of this trial?

This trial will test sargramostim, a medicine that helps the body produce more blood cells, in people with mild-to-moderate Alzheimer's disease. The goal is to see if it is safe and can slow down or improve symptoms of Alzheimer's. The medicine might help by boosting cells that protect or repair brain cells.

Research Team

Huntington Potter, PhD

Principal Investigator

University of Colorado Alzheimer's and Cognition Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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]

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]

References

1. England 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. [2018]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Sargramostim (rhu GM-CSF) as Cancer Therapy (Systematic Review) and An Immunomodulator. A Drug Before Its Time? [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Fulminant CNS perivascular lymphocytic proliferation: association with sargramostim, a hematopoietic growth factor. [2017]

4. United States pubmed.ncbi.nlm.nih.gov

Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor (rhu GM-CSF) as Adjuvant Therapy for Invasive Fungal Diseases. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

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

6. United States pubmed.ncbi.nlm.nih.gov

Comparison of hospitalization risk and associated costs among patients receiving sargramostim, filgrastim, and pegfilgrastim for chemotherapy-induced neutropenia. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Granulocyte macrophage colony-stimulating factor ameliorates DSS-induced experimental colitis. [2021]