G-CSF Treatment for Amyotrophic Lateral Sclerosis: A RCT Study Assessing Clinical Response

Granulocyte-Colony Stimulating Factor Treatment for Amyotrophic Lateral Sclerosis: A Randomized Control Trial Study Assessing Clinical Response

This study will examine the effectiveness of G-CSF in treating patients with amyotrophic lateral sclerosis (ALS) - a fatal neurological degenerative disease that causes adult-onset, progressive motor neurons loss in the spinal cord, brain stem and motor cortex. Patients develop progressive wasting and weakness of both upper and lower limbs, bulbar and respiratory muscles. Usually death from respiratory failure typically is within 3-5 years of diagnosis. Although there are various treatments for ALS, riluzole is the only approved treatment to delay the disease progression. G-CSF is an approved drug that is used to increase white blood cell counts. Moreover, G-CSF and its receptor are expressed by neurons. It acts anti-apoptosis by activating several protective pathways, stimulates neuronal differentiation of adult neural stem cells in the brain, and improves long-term recovery. G-CSF is a novel neurotrophic factor, and a highly attractive candidate for the treatment of neurodegenerative conditions such as ALS.

Patients 18 to 65 years of age who have had mild to moderately severe ALS for 0.5 to 2 years of duration may be eligible for this study. Candidates will be screened with a medical history and possible review of medical records, physical examination, blood test, urine and stool analyses, electrocardiogram, electrophysiological examination, neurological imaging and, for women, a pregnancy test.

Participants will have drug therapy according to randomized number. One group receives G-CSF while other group receives placebo. All of the participants receive riluzole treatment. For the procedure, patients are given a medication to lessen anxiety and any discomfort. Patients receive drug injections every 3 months for 5 days. The G-CSF dosage is 5μg/kg/day. Physical examination and interview, Appel ALS scale and ALS-Functional Rating Scale will be done in 14, 28 days and 3, 6, 9, 12 months. Electrophysiological examination will be tested per 3 months. Blood samples will be collected on treat 5, 14, 28 days and 3, 6, 9, 12 months.

Study Overview

• Status: Completed
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Drug: Granulocyte Colony Stimulating Factor; Drug: NS

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100083
      • Dongsheng Fan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• All subjects must have a verifiable diagnosis of ALS of 0.5 to 2 years' duration. The diagnosis must be supported by the Revised Criteria of the World Federation of Neurology. The grades of diagnosis must be clinically definite ALS or clinically probable ALS.
• All subjects must be over age 18 and below 65.
• The ALS is mildly to moderate based on ALS Health State Scale.
• Electrophysiological features show CMAP amplitude of motor nerve normal or mild declining.
• Serum creatine kinase is normal or mild upper, less than 500U/L.

Exclusion Criteria:

• If anyone of the above eligibility requirements is not met
• Use of any other investigational agent within 30 days beginning the treatment phase of this study
• Severe cardiac, pulmonary, hepatic or/and hematic disease
• HIV positivity or signs and symptoms consistent with HIV infection
• Pregnant or nursing women
• History of cancer with less than 5 years documentation of a disease-free state
• History of anaphylactic reaction or hypersensitivity to G-CSF or proteins derived from E.coli
• Alcohol or drug abuse in recent 1 year
• Can't understand or obey the rules of treatment
• Blood donor in recent 30 days

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1; 1,G-CSF,intervention	Drug: Granulocyte Colony Stimulating Factor; Granulocyte Colony Stimulating Factor,5ug/kg/day iH Qd*5 days,3 months interval for 4 times
Placebo Comparator: 2; 2,NS,intervention	Drug: NS; NS 1ml iH Qd*5 days, 3 months interval for 4 times

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
the mean rate of decline of ALS-FRS score	12 months

Secondary Outcome Measures

Outcome Measure	Time Frame
the mean rate decline of the AARS score	12 months

Collaborators and Investigators

• Sponsor: Peking University
• Investigators: Study Chair: Dongsheng Fan, MD, Peking University Third Hospital

Publications and helpful links

General Publications

• Fan DS, Zhang J, Deng M, Kang DX, Zheng JY, Xu YS, Lu M, Fu Y, Shen Y, Zhang YS, Zhang HG. [Basic and clinical researches on amyotrophic lateral sclerosis/motor neuron disease]. Beijing Da Xue Xue Bao Yi Xue Ban. 2009 Jun 18;41(3):279-81. Chinese.

Study record dates

Study Major Dates

• Study Start: December 1, 2006
• Study Completion (Actual): August 1, 2007

Study Registration Dates

• First Submitted: November 8, 2006
• First Submitted That Met QC Criteria: November 8, 2006
• First Posted (Estimate): November 9, 2006

Study Record Updates

• Last Update Posted (Estimate): November 28, 2007
• Last Update Submitted That Met QC Criteria: November 27, 2007
• Last Verified: November 1, 2007

More Information

Terms related to this study

• Keywords: Amyotrophic Lateral Sclerosis; Randomized Control Trial Study; Granulocyte Colony Stimulating Factor
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Sclerosis; Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Physiological Effects of Drugs; Immunologic Factors; Adjuvants, Immunologic; Lenograstim
• Other Study ID Numbers: R01-123456-1