What prior FDA approvals exist?

The FDA has approved several treatments for Alzheimer's Disease, including cholinesterase inhibitors like donepezil and galantamine, which help increase levels of acetylcholine in the brain, and memantine, which regulates glutamate activity. Recently, aducanumab, an anti-amyloid monoclonal antibody, was approved for its ability to reduce amyloid plaques in the brain. While these treatments differ in mechanism from Sargramostim, which is being studied for its potential immunomodulatory effects, they represent the current landscape of FDA-approved Alzheimer's therapies.

What other types of research exist?

Promising novel alternatives to Sargramostim for Alzheimer's Disease patients include: 1) Aducanumab, a monoclonal antibody targeting amyloid-beta plaques, approved by the FDA for AD treatment. 2) Lecanemab, another monoclonal antibody targeting amyloid-beta, which has shown positive results in clinical trials. 3) Donanemab, an investigational antibody targeting a modified form of amyloid-beta, currently in late-stage clinical trials. These therapies focus on reducing amyloid-beta plaques, a hallmark of Alzheimer's pathology.

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Cytokine

Sargramostim for Alzheimer's Disease (SESAD Trial)

Q: What side effects are associated with this type of intervention?

Common treatments for Alzheimer's Disease include cholinesterase inhibitors (e.g., donepezil, rivastigmine) and NMDA receptor antagonists (e.g., memantine). These treatments can cause side effects such as nausea, vomiting, diarrhea, dizziness, headache, and confusion. Sargramostim, a granulocyte-macrophage colony-stimulating factor, is being studied for its potential benefits in Alzheimer's. Known side effects of similar colony-stimulating factors include bone pain, fatigue, fever, and injection site reactions. It is important to discuss these potential side effects with a healthcare provider to manage and mitigate them effectively.

Phase 2

Recruiting

Led By Peter Pressman, MD

Research Sponsored by University of Colorado, Denver

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Have positive biomarker for brain amyloid pathology as shown by: Positive plasma assay for Aβ(42)/ Aβ(40) ratio AND Either positive CSF assay for AD assessment or positive amyloid PET, per PI read

Have a dedicated partner/caregiver informant who is in the company of the participant at least 12 hours a week, who can accompany them to scheduled visits, and who is able to provide accurate reporting upon the behavioral, cognitive and functional abilities of the participant

Must not have

Evidence of: Clinically significant pre-existing fluid retention (clinical or radiological); respiratory symptoms (e.g., dyspnea), moderate-to-severe lung disease (e.g. COPD, pulmonary infiltrates) cardiovascular symptoms or electrocardiographic evidence of cardiac disease that warrant therapeutic intervention (e.g., congestive heart failure, supraventricular arrhythmia, heart block, uncontrolled atrial fibrillation, etc.) a resting pulse less than 50, as reviewed by the study physician; prolonged QTc interval >470 ms in females, 450 ms in males). screening blood pressure measurement of greater than 160 systolic and/or 95 diastolic Known renal dysfunction or serum creatinine >150 μmol/L, or Glomerular Filtration Rate (GFR) less than 55 ml/min Known hepatic dysfunction (apart from Gilbert's syndrome) or serum ALT ≥3 times the upper limit of normal (ULN) Positive serology for hepatitis B surface antigen (HBs Ag), anti-hepatitis C virus (anti-HCV), anti-human immunodeficiency virus 1 and 2 antibodies (anti-HIV1 and anti-HIV2 Ab) or spirochetal infection (e.g. syphilis) Contraindication to lumbar dural puncture, including coagulopathy, concomitant anticoagulation therapy (except daily 81 mg aspirin), prior spinal surgery, significant deformity of the lumbar/sacral region, or any other factor that, in the opinion of the investigator, precludes safe LP procedure Contraindication or inability to complete magnetic resonance imaging (e.g., cardiac pacemaker/defibrillator, ferromagnetic metal implants) or PET scan Sensitivity to fluorodeoxyglucose F 18 Having past or planned exposure to ionizing radiation that would, together with the radiation resulting from the administrations of the PET tracer(s) used in this study, exceed applicable institutional, local, or national recommendations for annual or lifetime exposure Poor venous access Chronic use of non-steroidal anti-inflammatory drugs (NSAIDs), excepting 81 mg daily aspirin therapy Chronic use of an anti-cholinergic drug(s) Taking any prohibited medication or therapy Be the recipient of an investigational drug within 60 days of screening, or within 5 times the elimination half-life of that drug, whichever is the longest Prior treatment with an investigational anti-amyloid or anti-tauopathy therapy, or AD vaccine, unless it can be documented that they were on placebo Participation in the treatment phase of an investigational sargramostim clinical trial within 6-months of screening

History of deep vein thrombosis, pulmonary embolism, familial predisposition for deep vein thrombosis, or pulmonary embolism

Timeline

Screening 3 weeks

Treatment Varies

Follow Up informed consent to follow-up visit (38 weeks)

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Potential side effects of sargramostim may include allergic reactions, spleen enlargement, fluid retention issues like swelling or shortness of breath, blood disorders, and possible immune system changes.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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

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I have a caregiver who can be with me for at least 12 hours a week and attend visits.

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I am between 60 and 85 years old.

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My medications have been the same for the last 30 days.

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I have been diagnosed with mild or moderate Alzheimer's disease and my MoCA score is between 10-22.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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

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I have had seizures, not including febrile seizures as a baby.

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I haven't had cancer except for non-melanoma skin cancer in the last 5 years.

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My parent or sibling was diagnosed with Alzheimer's before 55.

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My BMI is 35 or higher.

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I am allergic to sargramostim, yeast products, certain drug components, or benzyl alcohol.

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I have had my spleen removed or it does not work properly.

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I have or have been treated for an autoimmune disease.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ informed consent to follow-up visit (38 weeks)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~informed consent to follow-up visit (38 weeks)

This trial's timeline: 3 weeks for screening, Varies for treatment, and informed consent to follow-up visit (38 weeks) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Safety as measured by number of Adverse Events (AEs) by body system

Secondary study objectives

Mini-Mental State Examination

Other study objectives

Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS-Cog13)

Alzheimer's Disease Cooperative Study -Activities of Daily Living Inventory (ADCS-ADL)

Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB)

+6 more

Side effects data

From 2021 Phase 4 trial • 87 Patients • NCT04326920

22%

Infectious disorder (not COVID-19)

15%

Constipation

Cardiac disorder

Epistaxis

Multi-bacterial bacteremia causing hemorrhagic shock

Pneumonia

Respiratory failure

Hypoxia

Thormboembolic event

Aspergillus infection

100%

80%

60%

40%

20%

Study treatment Arm

Control Group

Active Sargramostim Treatment Group

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: SargramostimExperimental Treatment1 Intervention

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

Group II: Placebo Control - SalinePlacebo Group1 Intervention

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

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Sargramostim

2006

Completed Phase 4

~850

0 / 14Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Alzheimer's Disease (AD) include cholinesterase inhibitors (donepezil, rivastigmine, galantamine) and NMDA receptor antagonists (memantine). Cholinesterase inhibitors work by preventing the breakdown of acetylcholine, a neurotransmitter important for learning and memory, thereby enhancing cholinergic transmission. NMDA receptor antagonists, like memantine, regulate glutamate activity to prevent excitotoxicity, which can damage neurons. These mechanisms are crucial as they aim to improve cognitive function and slow symptom progression in AD patients. Sargramostim, a granulocyte-macrophage colony-stimulating factor, is being studied for its potential to modulate immune responses and reduce neuroinflammation, which may offer a novel approach to treating AD by addressing underlying inflammatory processes.