To Evaluate the Efficacy and Safety/Tolerability Profiles of G-CSF in Subjects With Mild to Moderate Alzheimer's Disease
Condition: Alzheimer's Disease
MeSH terms: Alzheimer Disease
Study type: Interventional
Phase: Phase 2

Summary: 
      With the enrichment of living environment and the progress of medicine, the scale of aging
      population has increased in many countries of the world. Alzheimer's disease (AD), the
      leading cause of dementia, counts for approximately 60% to 70% in dementia in aged
      population. AD is a well-known neurodegenerative disease and characterized by the formation
      of neurofibrillary tangles and deposition of amyloid in the brain. It also affects more than
      12 million patients worldwide and puts a tremendous burden on family caregivers and causes
      high nursing home costs for society. So far, the mechanisms of AD have not been elucidated
      and currently no curable treatment exists. Thus, clinical trials concerning the treatment of
      AD are in urgent expectation.

      Granulocyte-colony stimulating factor (G-CSF) is a growth factor that presents in human body
      in small quantity and is known to promote the blood cell proliferation and differentiation.
      Previous studies showed injection of G-CSF could help release hematopoietic stem cell (HSCs)
      from bone marrow to the peripheral blood, and then migrate to repair damaged areas, e.g.
      heart tissue and ischemia brain tissue. We have found that G-CSF triggering release of stem
      cells from bone marrow shows the potential as an effective reagent for treatment of AD by
      using two AD mouse models. The one was generated by injecting the brains of normal mice with
      amyloid and another was by using a strain of transgenic mice which naturally exhibit
      Alzheimer's disease-like neuronal apoptosis and memory loss. Subcutaneous administration of
      G-CSF into mice significantly rescued their cognitive/memory functions.

      G-CSF has already been widely used in clinical practice, for example, neutropenia caused by
      chemotherapy in cancer and bone marrow transplantation. The new finding shows G-CSF can
      release HSCs from bone marrow and these cells not only can pass through the blood-brain
      barrier but can selectively migrate to the region of damaged brain to improve neurological
      recovery. Thus, we conduct this clinical trial to investigate the potential effect of G-CSF
      for the cognitive function of AD patients. If successful, G-CSF could open up a new window
      for AD treatment which is less invasive and more effective than the current therapies.
    

Detailed description: 
      This is a randomized open-label Phase 2 trial with parallel design using no-treatment group
      as control. Subjects in the treatment arm will receive subcutaneous G-CSF with the dosage of
      10 microgram/kg/day, for 5 continuous days in the first week. The second dosage will be given
      in the 12 week. If subjects has received Donepezil already, the Donepezil will be
      concomitantly used in a stable dose (the same dose as pre-entering this study) during the
      study.

      Background data and general medical history will be registered on the screening visit (Visit
      1, started four weeks or less before Visit 2). Subjects fulfil the inclusion criteria 1) age
      between 50 to 85 years old; 2) those who were diagnosed as AD and the supporting evidences
      from the brain computed tomography or Magnetic Resonance Imaging scan within 12-months; 3)
      Mini-Mental State Examination scores of 10 to 26, and, 4) Clinical Dementia Rating score of 1
      or 2. Subjects with clinically significant medical or neurological disorders, other than AD,
      that may affect cognition will be excluded Additional inclusion criteria included Modified
      Hachinski Ischemic score of ≤ 4, Hamilton Psychiatric Rating Scale for Depression score of ≤
      12and a reliable caregiver who is sufficiently familiar with the subject and is willing to
      provide the accurate data.

      Participants will receive standard physical examination in all visits. Serum tests include
      complete blood count (CBC),total bilirubin, creatinine, blood urea nitrogen (BUN), uric acid,
      aspartate transaminase (AST), alanine transaminase (ALT), total protein, albumin, Vitamin
      B12, folate, T4, thyroid-stimulating hormone (TSH), HbA1c, rapid plasmin reagin
      (RPR)/Treponema pallidum haemagglutination (TPHA) will be also obtained.
    

Intervention name(s): Filgrastim (75mcg/0.3ml)
Intervention type(s): Drug
Intervention description(s): Subjects who meet all eligible requirements for entry into the study will be randomized into one of the two treatment groups in 1:1 ratio as shown below:
10 microgram/kg/day, by sc, for 5 continuous days for the first week, rest for 11 weeks; repeat dosing regimen every 12-weekly (12 weeks / cycle) for 2 cycles
Non-treatment
Other intervention name(s): NEUPOGEN®
Intervention MeSH terms: Lenograstim
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Dementia; Alzheimer's disease; Granulocyte-colony stimulating factor