Efficacy and Safety of Filgrastim in Alzheimer's Disease

Alzheimer's Disease Clinical Trial

— FFAD  

Official title:

Efficacy and Safety of Filgrastim as a Pro‐Cognitive Agent in Alzheimer's Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01617577
• Other study ID #: ADDF-GCSF
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: November 8, 2011
• Last updated: November 26, 2012
• Start date: June 2009
• Est. completion date: February 2012

Study information

• Verified date: June 2012
• Source: University of South Florida
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: February 2012
• Est. primary completion date: February 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 55 Years and older

Eligibility

Inclusion Criteria:

• People with probable AD (by NINDS/ADRDA criteria) who are likely to be testable at the conclusion of the study period, and who do not have concurrent medical conditions or medications that might influence cognitive testing or that would increase the risk of treatment

• The participants will have a Min Mental State Examination score of between 10 and 24

• stable medical condition and stable medications for 3 months prior to screening

• study partner (spouse or caregiver) to accompany patient to all scheduled visits; able to complete baseline assessments

• physically acceptable for this study as confirmed by medical history, physical exam, neurological exam and clinical tests

Exclusion Criteria:

• clinically significant cardiac arrhythmia

• history of clinically significant stroke

• use of another investigational drug within 2 months of screening

• current evidence or history in the past 2 years of epilepsy, focal brain lesion, head injury with loss of consciousness or DSM-IV criteria for any major psychiatric disorder including psychosis, major depression, bipolar disorder alcohol or substance abuse; residence in a skilled nursing facility (but patients in assisted living facility are acceptable)

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease

Intervention

Drug:
• G-CSF; filgrastim
The drug is administered s.c. at a dose of 10 microg/kg daily for 5 days
• Placebo
vehicle (D5W or 5% dextrose solution) is administered subcutaneously daily for 5 days

Locations

Country	Name	City	State
United States	USF/Byrd Alzheimer's Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
University of South Florida

Country where clinical trial is conducted

United States, 

References & Publications (1)

Sanchez-Ramos J, Song S, Sava V, Catlow B, Lin X, Mori T, Cao C, Arendash GW. Granulocyte colony stimulating factor decreases brain amyloid burden and reverses cognitive impairment in Alzheimer's mice. Neuroscience. 2009 Sep 29;163(1):55-72. doi: 10.1016/j.neuroscience.2009.05.071. Epub 2009 Jun 14. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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,	Baseline and 2wk and 4 wk after Rx;	No
Primary	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,	Baseline and final visit (14 wks)	No

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