Efficacy and Safety of Filgrastim in Alzheimer's Disease (FFAD)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of South Florida
ClinicalTrials.gov Identifier:
NCT01617577
First received: November 8, 2011
Last updated: November 26, 2012
Last verified: June 2012
  Purpose

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.


Condition Intervention Phase
Alzheimer's Disease
Drug: G-CSF; filgrastim
Drug: Placebo
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Efficacy and Safety of Filgrastim as a Pro‐Cognitive Agent in Alzheimer's Disease

Resource links provided by NLM:


Further study details as provided by University of South Florida:

Primary Outcome Measures:
  • Cognitive Measures Incluing ADAScog, Selected CANTABS Tests (Paired Associate Learning (PAL)and PAL ) [ Time Frame: Baseline and 2wk and 4 wk after Rx; ] [ Designated as safety issue: No ]

    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,


  • Cognitive Measures Incluing ADAScog, Selected CANTABS Tests (Paired Associate Learning (PAL)and PAL ) [ Time Frame: Baseline and final visit (14 wks) ] [ Designated as safety issue: No ]

    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,



Enrollment: 8
Study Start Date: June 2009
Study Completion Date: February 2012
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: G-CSF (filgrastim) first phase
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
The drug is administered s.c. at a dose of 10 microg/kg daily for 5 days
Other Name: Neupogen; granulocyte colony stimulating factor (GCSF)
Placebo Comparator: Placebo first phase
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
vehicle (D5W or 5% dextrose solution) is administered subcutaneously daily for 5 days
Other Name: Vehicle (5% dextrose water or D5W)

Detailed 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.

  Eligibility

Ages Eligible for Study:   55 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01617577

Locations
United States, Florida
USF/Byrd Alzheimer's Center
Tampa, Florida, United States, 33612
Sponsors and Collaborators
University of South Florida
  More Information

Additional Information:
Publications:
Responsible Party: University of South Florida
ClinicalTrials.gov Identifier: NCT01617577     History of Changes
Other Study ID Numbers: ADDF-GCSF
Study First Received: November 8, 2011
Results First Received: June 29, 2012
Last Updated: November 26, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by University of South Florida:
G-CSF
granulocyte colony stimulating factor
Filgrastim

Additional relevant MeSH terms:
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Lenograstim
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 18, 2014