A Phase 1/2 interventional study of G-CSF; filgrastim and Placebo in Alzheimer's Disease, sponsored by University of South Florida. Completed at 1 site in United States. Open to participants aged 55 Years and older. Per ClinicalTrials.gov, last updated 2012-12-27.
Sponsored by University of South Florida · Phase 1/2, Interventional, and Treatment
Filgrastim (G-CSF) is widely used for treatment of patients who have a deficiency of white blood cells. It is also routinely used to stimulate and mobilize stem/progenitor cells for bone marrow transplantation. In studies of thousands of healthy donor subjects treated with G-CSF, the side-effects profile has been reported to be mild and reversible. Currently, G-CSF is under investigation in clinical trials in Germany and the US that aim to enhance recovery from strokes and heart attacks. In animal studies, G-CSF has been observed to improve cognitive performance and to markedly reduce amyloid deposition in hippocampus and entorhinal cortex in a mouse model of Alzheimer's Disease (AD). Since this drug is being used safely in many people throughout the world, the investigators hypothesize that it will also be safe to give to patients with Alzheimer's disease and that it may improve some aspects of memory and thinking. The present pilot study has two goals or objectives: 1) to investigate the effects of a five day schedule of Filgrastim administration on cognitive function and 2) to assess its tolerability and safety in a small group (12 patients) with mild to moderate stage AD. Patients who are eligible for the study will be randomly assigned to one of two groups (n=6 per group). One group will receive a five-day course of Filgrastim injections and the other group of subjects will receive vehicle injections (solution without drug). At the end of the first phase of the study (week 8), the groups will cross over to receive either vehicle or Filgrastim as appropriate. In this way all subjects will have received the active medication by the end of the study. After the study is finished the investigators should know whether or not Filgrastim improves some aspects of thinking and memory. And the investigators should know whether or not it is safe to give this medication to patients with Alzheimer's disease. To ensure that the drug is safe, a Safety Monitoring Committee will oversee the entire study. They will review all laboratory data, including complete blood counts, serum chemistry, EKGs and adverse events.
The study was originally designed to have two arms (GCSF first followed by placebo= Arm 1; placebo followed by GCSF=Arm2). Total length of study for each subject was 14 weeks, with crossover on week 7.
Linear regression models could not be used because of the small number of subjects; n = 5 in the first Arm who received G-CSF before crossover to the placebo phase and n = 3 in Arm 2 (who received placebo first before crossover to the G-CSF treatment phase). The general rule for the sample size required for regression analysis is n = 15 per covariate. Therefore, comparison of the final cognitive scores on visit 5 (week 14) were compared to scores at baseline (visit 1) for all subjects (n = 8) using the Wilcoxon signed rank test. Plasma cytokine changes were plotted to compare effects following G-CSF to that following placebo, regardless of the order of treatment. Wilcoxon sum rank test was used to test differences between G-CSF treatment and placebo treatment at specific intervals after treatment. Statistical Package for the Social Sciences (SPSS Version 19) was used for all data analysis.
3,678 studies on the registry are indexed under Alzheimer Disease; 872 are open to participants now.
This study's enrollment of 8 is below the median of 70 across 2,808 interventional studies indexed under Alzheimer Disease.
Browse Alzheimer Disease studies →University of South Florida is the lead sponsor of 333 studies on the registry; 63 are open to participants now.
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Exclusion Criteria:
Subjects assigned to this arm receive G-CSF for 5 days during the first phase of the study. At week 7 these subjects cross over to receive placebo injections for five days
Drug: G-CSF; filgrastim
Subjects assigned to this arm receive placebo injections daily for 5 days; after wk 7 they crossover to receive 5 daily injections of injections of G-CSF.
Drug: Placebo
The drug is administered s.c. at a dose of 10 microg/kg daily for 5 days
Also known as: Neupogen; granulocyte colony stimulating factor (GCSF)
vehicle (D5W or 5% dextrose solution) is administered subcutaneously daily for 5 days
Also known as: Vehicle (5% dextrose water or D5W)
Cognitive Measures Incluing ADAScog, Selected CANTABS Tests (Paired Associate Learning (PAL)and PAL )
Scores from each of the cognitive assessments: mean ADAScog: a decrease in total score units = improvement, min=0 max=31 mean PAL (memory): an increase in score = improvement, min= 0 max=12 mean PAL (total trial adj): a decrease in score = improvement,
Time frame: Baseline and 2wk and 4 wk after Rx;
Cognitive Measures Incluing ADAScog, Selected CANTABS Tests (Paired Associate Learning (PAL)and PAL )
Scores from each of the cognitive assessments: mean ADAScog: a decrease in total score units = improvement, min=0 max= mean PAL (memory): an increase in score = improvement, mean PAL (total trial adj): a decrease in score = improvement,
Time frame: Baseline and final visit (14 wks)
| Milestone | G-CSF First Phase | Placebo First Phase |
|---|---|---|
| Started | 5 | 3 |
| Completed | 5 | 3 |
| Not completed | 0 | 0 |
Scores from each of the cognitive assessments: mean ADAScog: a decrease in total score units = improvement, min=0 max=31 mean PAL (memory): an increase in score = improvement, min= 0 max=12 mean PAL (total trial adj): a decrease in score = improvement,
| units on a scale | G-CSF | Placebo |
|---|---|---|
| ADAScog Baseline | 22.25 ± 2.49 | 22.25 ± 2.49 |
| ADAScog 2wk post Rx | 20.5 ± 1.67 | 17.75 ± 2.67 |
| ADAScog 4wks post Rx | 21.5 ± 2.507 | 20.125 ± 2.14 |
| PALmem baseline | 2.75 ± 0.59 | 2.75 ± 0.59 |
| PALmem 2wk post Rx | 4.14 ± 0.857 | 3.75 ± 1.06 |
| PALmem 4wk post RX | 5.50 ± 1.477 | 4.75 ± 0.881 |
| PAL (tot trial adj) baseline | 33.87 ± 3.02 | 33.87 ± 3.02 |
| PAL (tot trial adj) 2wk post Rx | 28.48 ± 6.16 | 33.62 ± 4.26 |
| PAL(tot trial adj) 4wk post RX | 24.45 ± 5.36 | 30.62 ± 3.02 |
Scores from each of the cognitive assessments: mean ADAScog: a decrease in total score units = improvement, min=0 max= mean PAL (memory): an increase in score = improvement, mean PAL (total trial adj): a decrease in score = improvement,
| units on a scale | G-CSF and Placebo |
|---|---|
| ADAScog Baseline | 24 ± 2.86 |
| ADAScog 14wks post Rx | 20.37 ± 2.25 |
| PALmem baseline | 2.85 ± 0.67 |
| PALmem 14wk post RX | 5.17 ± 1.41 |
| PAL (tot trials adj) baseline | 33.88 ± 3.003 |
| PAL (tot trials adj) 14wk post RX | 30. ± 3.65 |
Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Placebo | — | 0/8 (0%) | 4/8 (50%) |
| G-CSF | — | 0/8 (0%) | 5/8 (62.5%) |
| Event | Placebo | G-CSF |
|---|---|---|
| generalized achesMusculoskeletal and connective tissue disorders | 2/8 | 5/8 |
| back painMusculoskeletal and connective tissue disorders | 4/8 | 3/8 |
| headacheNervous system disorders | 1/8 | 1/8 |
| nauseaNervous system disorders | 1/8 | 1/8 |
| visual hallucinationsNervous system disorders | 1/8 | 0/8 |
| Age, Categorical(Participants) | G-CSF First Phase | Placebo First Phase | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 3 | 1 | 4 |
| >=65 years | 2 | 2 | 4 |
| Age Continuous(years) | G-CSF First Phase | Placebo First Phase | Total |
|---|---|---|---|
| Mean | 71.6 ± 3.8 | 75.2 ± 3.1 | 72.3 ± 2.9 |
| Sex: Female, Male(Participants) | G-CSF First Phase | Placebo First Phase | Total |
|---|---|---|---|
| Female | 2 | 1 | 3 |
| Male | 3 | 2 | 5 |
| Region of Enrollment(participants) | G-CSF First Phase | Placebo First Phase | Total |
|---|---|---|---|
| United States | 5 | 3 | 8 |
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