Efficacy and Safety of Filgrastim in Alzheimer's Disease

NCT01617577 | Completed Phase 1 Results DMC

• 1 other identifier: ADDF-GCSF
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Alzheimer's Disease

Keywords

G-CSF; granulocyte colony stimulating factor; Filgrastim

Outcome Measures

Primary Outcomes (2)

• 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;

• 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)

Study Arms (2)

G-CSF (filgrastim) first phase

EXPERIMENTAL

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

Placebo first phase

PLACEBO COMPARATOR

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

Interventions

G-CSF; filgrastim DRUG

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)

G-CSF (filgrastim) first phase

Placebo DRUG

vehicle (D5W or 5% dextrose solution) is administered subcutaneously daily for 5 days

Also known as: Vehicle (5% dextrose water or D5W)

Placebo first phase

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• University of South Florida: lead

Study Sites (1)

USF/Byrd Alzheimer's Center

Tampa, Florida, 33612, United States

Location

Related 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.

  PMID: 19500657 BACKGROUND

Related Links

• Related Info

MeSH Terms

Conditions

Alzheimer Disease

Interventions

Granulocyte Colony-Stimulating Factor; Filgrastim

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: Professor Juan Sanchez-Ramos
• Organization: University of South Florida

jsramos@health.usf.edu

813-974-5841

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 8, 2011
• First Posted: June 12, 2012
• Study Start: June 1, 2009
• Primary Completion: February 1, 2012
• Study Completion: February 1, 2012
• Last Updated: December 27, 2012
• Results First Posted: December 27, 2012

Record last verified: 2012-06

Locations

US (1)