Down SyndromePhase 2NCT05482334
Trial to Evaluate Safety and Efficacy of GM-CSF /Sargramostim in Down Syndrome
A Phase 2 study testing Sargramostim for Injection in people with Down Syndrome, run by University of Colorado, Denver at 1 site in United States.
Trial summary
This trial protocol is designed to evaluate primarily whether the use of sargramostim (recombinant human GM-CSF), administered five days per week for four consecutive weeks (20 treatment days), will be well tolerated by and safe for use in young adult participants with Down syndrome. Read more about this study
- Who is it for?
- Ages 18 to 35 years
- Conditions the study is for
- Down Syndrome
- What is being tested?
- Sargramostim for Injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 23 Oct 2023to Sep 2026
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 18 to 35 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Males or females with Down syndrome between 18-35 years of age.
- A cytogenetic diagnosis of full trisomy 21 or complete unbalanced translocation of chromosome 21.
- 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.
- Be willing / able to provide written informed consent or assent. If assent is provided, consent must be provided by a legally authorized representative (LAR), who may or may not be the dedicated study partner / caregiver. Documentation of LAR status will follow local laws and regulations.
- Be physically able to participate by medical history, clinical exam, and other testing, with adequate visual acuity and auditory discrimination.
- Must reside within a proximity of the study site that will not preclude their regularly scheduled participation in the trial.
Show all 9Show fewer
- Be willing to avoid pregnancy or fathering children for the duration of the study.
- Must have received recent testing for hypothyroidism during the past 6 months, and if positive for hypothyroidism, they must be stable on medications for treating hypothyroidism for at least 30 days prior to enrollment, and they must remain on their hypothyroidism treatments for the duration of the trial.
- Be stable on all other medications for at least 30 days prior to initial screening visit.
Who cannot join
- Pregnant or breastfeeding female, or female of childbearing potential and not protected by highly effective contraceptive method of birth control (i.e., oral or depot contraceptives or intrauterine device [IUD] or participant was surgically sterilized) and/or unwilling or unable to be tested for pregnancy; Male refusing to use condoms, if partner can get pregnant.
- Vaccination with live attenuated virus within six weeks of inclusion in the study or planned during the study.
- 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).
- Active cancer / malignant neoplasm within five years of screening other than nonmelanoma skin cancers (e.g., basal cell or squamous cell). Previous diagnosis of leukemia, despite remission state or length of time, is exclusionary.
- Poor venous access not allowing repeated blood tests.
- History of a latex or yeast allergy.
Show all 25Show fewer
- Presence/history of drug hypersensitivity; or known hypersensitivity to sargramostim, yeast-derived products, any other component of the product, or benzyl alcohol (present in bacteriostatic water or saline for injection).
- Concomitant treatment with other immunosuppressants (e.g., corticosteroids, methotrexate).
- History of deep vein thrombosis, pulmonary embolism, familial predisposition for deep vein thrombosis, or pulmonary embolism.
- History of asplenia, hyposplenia, or splenectomy (for any indication).
- Untreated or unstable medical condition that could interfere with the study assessments in the opinion of the study physician, or that may require immune-stimulating, immunesuppressive, or immune-modulating treatment(s) during the conduct of the study (e.g., therapeutic vaccines, cytokines, anti-cytokine monoclonal antibodies, etc.)
- History of seizures (except infant febrile seizures).
- Evidence of:
- 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 assessed by the study physician;
- prolonged QTc interval greater than 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 greater than 150 micromoles/L, or Glomerular Filtration Rate (GFR) less than 55 ml/min.
- Known hepatic dysfunction (apart from Gilbert's syndrome) or serum ALT greater than or equal to 3 times the upper limit of normal (ULN).
- Contraindication or inability to complete magnetic resonance imaging (e.g., cardiac pacemaker/defibrillator, ferromagnetic metal implants).
- Chronic use of non-steroidal anti-inflammatory drugs (NSAIDs), excepting 81 mg daily aspirin therapy. Note: For the purposes of this protocol, chronic use is defined as the weekly usage of an NSAID drug for three or more times per week and for two or more weeks within any four-week period.
- Chronic use of an anti-cholinergic drug. Note: For the purposes of this protocol, chronic use is defined as the weekly usage of an anti-cholinergic drug for three or more times per week and for two or more weeks within any four-week period.
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Colorado Anschutz Medical Campus
Aurora, Colorado, 80045
About this study
Official title: Phase II Trial to Evaluate Safety and Efficacy of GM-CSF /Sargramostim in Down Syndrome
This trial protocol is designed to evaluate primarily whether the use of sargramostim (recombinant human GM-CSF), administered five days per week for four consecutive weeks (20 treatment days), will be well tolerated by and safe for use in young adult participants with Down syndrome.
Read the detailed description
This trial protocol is designed to evaluate primarily whether the use of sargramostim (recombinant human GM-CSF), administered five days per week (250 μg/m2/day subcutaneously) for four consecutive weeks (20 treatment days), will be well tolerated by and safe for use in young adult participants (age 18-35) with Down Syndrome; Secondarily whether sargramostim will have an impact on cognition, and exploratory whether sargramostim has an impact upon activities of daily and quality of life, and impact upon several biomarkers associated with DS, as evaluated by multimodal neuroimaging techniques and blood analyses.
- Conditions
- Down Syndrome
- Being tested
- Sargramostim for Injection, Saline Placebo
- Keywords
- Down syndrome, Trisomy 21
- Medical subject headings
- Down Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sargramostim for InjectionDrug
Also called Leukine, Granulocyte Macrophage Colony Stimulating Factor
Recombinant human GM-CSF
Saline PlaceboDrug
Also called Bacteriostatic Saline
Bacteriostatic Saline
| Study group | Role | What they receive |
|---|---|---|
| Sargramostim | Experimental | Sargramostim 250 μg/m2/day subcutaneously (5 days per week) Receives: Drug: Sargramostim for Injection |
| Placebo Control - Saline | Placebo comparator | Placebo equivalent volume subcutaneously (5 days per week) Receives: Drug: Saline Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety as measured by number of Adverse Events (AEs) by body system
The safety of sargramostim will be assessed through number of adverse events (AEs) by body system from consent to follow-up within a safety analysis set consisting of all individuals who were enrolled and and randomized and who received at least one injection of sargramostim or placebo.
Measured: Informed consent to Follow-up Visit (20 weeks)
Secondary outcomes (1)
Down syndrome Mental Status Exam (DSMSE)
The DSMSE provides a broad assessment of cognitive function specially designed for use within the population of individuals with Down syndrome. Similar to the MMSE, the range for scores in the DMSE is from 0 to 30, with lower scores indicating greater impairment.
Measured: Baseline to End of Treatment, Follow-up (20 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Aug 2022
- Study start23 Oct 2023
- Primary completionSep 2026 (estimated)
- Study completionSep 2026 (estimated)
Why it stopped: Difficulties enrolling participants due to study design
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Down SyndromeStudies 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
- Model description
- IP vs Placebo
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Responsible party
- Sponsor
- Investigators
- Peter Pressman, MD, Principal investigator, CU Alzheimer's and Cognition Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05482334
- Sponsor's protocol ID
- 22-1301
- Other IDs
- 1R61AG074859-01
- Status last verified
- Mar 2025
- First submitted
- 28 Jul 2022
- Last updated
- 2 Apr 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Potter H, Woodcock JH, Boyd TD, Coughlan CM, O'Shaughnessy JR, Borges MT, Thaker AA, Raj BA, Adamszuk K, Scott D, Adame V, Anton P, Chial HJ, Gray H, Daniels J, Stocker ME, Sillau SH. Safety and efficacy of sargramostim (GM-CSF) in the treatment of Alzheimer's disease. Alzheimers Dement (N Y). 2021 Mar 24;7(1):e12158. doi: 10.1002/trc2.12158. eCollection 2021.
PubMed 33778150Ahmed MM, Wang AC, Elos M, Chial HJ, Sillau S, Solano DA, Coughlan C, Aghili L, Anton P, Markham N, Adame V, Gardiner KJ, Boyd TD, Potter H. The innate immune system stimulating cytokine GM-CSF improves learning/memory and interneuron and astrocyte brain pathology in Dp16 Down syndrome mice and improves learning/memory in wild-type mice. Neurobiol Dis. 2022 Jun 15;168:105694. doi: 10.1016/j.nbd.2022.105694. Epub 2022 Mar 18.
PubMed 35307513
Study at a glance
From the registry record, last updated by the sponsor on 2 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial to Evaluate Safety and Efficacy of GM-CSF /Sargramostim in Down Syndrome
- ClinicalTrials.gov ID
- NCT05482334
- Acronym / sponsor ID
- 22-1301
- Conditions
- Down Syndrome
- Keywords
- Down syndrome, Trisomy 21
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Difficulties enrolling participants due to study design
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Study start
- 23 Oct 2023 (actual)
- Primary completion
- Sep 2026 (estimated)
- Study completion
- Sep 2026 (estimated)
- First posted
- 1 Aug 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This trial protocol is designed to evaluate primarily whether the use of sargramostim (recombinant human GM-CSF), administered five days per week for four consecutive weeks (20 treatment days), will be well tolerated by and safe for use in young adult participants with Down syndrome.
Detailed description
This trial protocol is designed to evaluate primarily whether the use of sargramostim (recombinant human GM-CSF), administered five days per week (250 μg/m2/day subcutaneously) for four consecutive weeks (20 treatment days), will be well tolerated by and safe for use in young adult participants (age 18-35) with Down Syndrome; Secondarily whether sargramostim will have an impact on cognition, and exploratory whether sargramostim has an impact upon activities of daily and quality of life, and impact upon several biomarkers associated with DS, as evaluated by multimodal neuroimaging techniques and blood analyses.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- IP vs Placebo
| Arm | Type | Receives |
|---|---|---|
| Sargramostim | Experimental | Drug: Sargramostim for InjectionSargramostim 250 μg/m2/day subcutaneously (5 days per week) |
| Placebo Control - Saline | Placebo comparator | Drug: Saline PlaceboPlacebo equivalent volume subcutaneously (5 days per week) |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- Males or females with Down syndrome between 18-35 years of age.
- A cytogenetic diagnosis of full trisomy 21 or complete unbalanced translocation of chromosome 21.
- 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.
- Be willing / able to provide written informed consent or assent. If assent is provided, consent must be provided by a legally authorized representative (LAR), who may or may not be the dedicated study partner / caregiver. Documentation of LAR status will follow local laws and regulations.
- Be physically able to participate by medical history, clinical exam, and other testing, with adequate visual acuity and auditory discrimination.
Key exclusion criteria (25 listed)
- Pregnant or breastfeeding female, or female of childbearing potential and not protected by highly effective contraceptive method of birth control (i.e., oral or depot contraceptives or intrauterine device [IUD] or participant was surgically sterilized) and/or unwilling or unable to be tested for pregnancy; Male refusing to use condoms, if partner can get pregnant.
- Vaccination with live attenuated virus within six weeks of inclusion in the study or planned during the study.
- 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).
- Active cancer / malignant neoplasm within five years of screening other than nonmelanoma skin cancers (e.g., basal cell or squamous cell). Previous diagnosis of leukemia, despite remission state or length of time, is exclusionary.
- Poor venous access not allowing repeated blood tests.
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 |
|---|---|---|
| Sargramostim for InjectionAlso: Leukine, Granulocyte Macrophage Colony Stimulating FactorRecombinant human GM-CSF | Drug | Sargramostim |
| Saline PlaceboAlso: Bacteriostatic SalineBacteriostatic Saline | Drug | Placebo Control - Saline |
Primary outcome
Safety as measured by number of Adverse Events (AEs) by body system
Time frame: Informed consent to Follow-up Visit (20 weeks)
The safety of sargramostim will be assessed through number of adverse events (AEs) by body system from consent to follow-up within a safety analysis set consisting of all individuals who were enrolled and and randomized and who received at least one injection of sargramostim or placebo.
1 secondary outcome
Down syndrome Mental Status Exam (DSMSE)
Time frame: Baseline to End of Treatment, Follow-up (20 weeks)
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Apr 2025.
- Results publication: PubMed 33778150Potter H, Woodcock JH, Boyd TD, Coughlan CM, O'Shaughnessy JR, Borges MT, Thaker AA, Raj BA, Adamszuk K, Scott D, Adame V, Anton P, Chial HJ, Gray H, Daniels J, Stocker ME, Sillau SH. Safety and efficacy of sargramostim (GM-CSF) in the treatment of Alzheimer's disease. Alzheimers Dement (N Y). 2021 Mar 24;7(1):e12158. doi: 10.1002/trc2.12158. eCollection 2021.
- Results publication: PubMed 35307513Ahmed MM, Wang AC, Elos M, Chial HJ, Sillau S, Solano DA, Coughlan C, Aghili L, Anton P, Markham N, Adame V, Gardiner KJ, Boyd TD, Potter H. The innate immune system stimulating cytokine GM-CSF improves learning/memory and interneuron and astrocyte brain pathology in Dp16 Down syndrome mice and improves learning/memory in wild-type mice. Neurobiol Dis. 2022 Jun 15;168:105694. doi: 10.1016/j.nbd.2022.105694. Epub 2022 Mar 18.
Related trials for Down Syndrome
Not yet recruitingPhase 4
Oral Switch in Bloodstream Infections in Immunocompromised Children
Bloodstream Infection, Bloodstream Infection Due to Central Venous Catheter
Not yet recruiting
Fecal Microbiota Transplantation (FMT) to Slow Biological Aging
Aging, Healthy, Aging and Cognitive Health
Active, not recruitingPhase 3
A Study to Investigate Blinatumomab in Combination With Chemotherapy in Patients With Newly Diagnosed B-Lymphoblastic Leukemia
B Acute Lymphoblastic Leukemia, B Lymphoblastic Lymphoma
Not yet recruiting
Executive Function Play Opportunities for Children With Down Syndrome
Down Syndrome, Trisomy 21
RecruitingObservational study
Natural History of Dysregulation and Aging of the Immune System in People With Trisomy 21 With and Without Thymectomy
Down Syndrome
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.
Peter Pressman, MD principal investigator
CU Alzheimer's and Cognition Center
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 Sargramostim for Injection in people with Down Syndrome, 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 9 inclusion and 25 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: withdrawn, as of the sponsor's last update on 2 Apr 2025. 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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Safety as measured by number of Adverse Events (AEs) by body system (time frame: Informed consent to Follow-up Visit (20 weeks)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05482334, which also lists 2 linked publications.
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 Apr 2025.