Clinical trial NCT00404014: Study to Evaluate Safety, Tolerability, and Effect of AL208 on Mild Cognitive Impairment Following Coronary Artery Bypass Graft Surgery
Official title: A Phase II Study Designed to Evaluate the Safety, Tolerability, and Effect of a Single, Rising Dose of Intravenous AL-208, Followed by a Placebo-Controlled, Double-Blind, Parallel-Group Evaluation of a Single Dose of AL-208, on Mild Cognitive Impairment Following Coronary Artery Bypass Graft Surgery.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Mild Cognitive Impairment
Keywords: MCI following CABG surgery
Lead sponsor: Allon Therapeutics
Sponsor class: INDUSTRY
First posted: 2006-11-27
Enrollment: 234
Sex: ALL
Minimum age (years): 50
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The primary objective is to compare mild cognitive impairment in the AL-208 group with the placebo group at 14 + - 3 days after CABG surgery


Eligibility criteria: Inclusion Criteria:

1. Males and females (of non-childbearing potential), 50 to 79 years of age.
2. Undergoing CABG surgery with the use of extracorporeal circulation.
3. Willing and able to complete cognitive testing.
4. Score \< 16 on the Center for Epidemiological Studies in Depression scale (CES-D).
5. Score \> or = 28 on the Mini-Mental State Examination (MMSE).
6. Willing and able to provide informed consent to participate in this study
7. Fluency in written and spoken English.

Exclusion Criteria:

1. Presence of any severe mental illness that could affect interpretation of efficacy data, such as schizophrenia or bipolar affective disorder; any untreated or unstable psychiatric condition including depressive disorder or anxiety disorder.
2. History of stroke or other significant neurological disorder
3. Transient ischemic attack (TIA) with ongoing cognitive sequelae
4. Chronic atrial fibrillation or uncontrolled atrial fibrillation prior to surgery
5. Myocardial infarction (MI) within the last 8 weeks and/or previous history of more than 3 MIs
6. History of liver dysfunction with ongoing sequelae (including but not limited to liver enzymes \> 2.5 x upper limit or normal (ULN) at screening).
7. History of renal dysfunction with ongoing sequelae (including but not limited to creatinine value \> 2.5 mg/dL at screening).
8. Known active alcohol or drug abuse.
9. Concurrent use of prescription medications known to enhance memory
10. General anesthesia (defined as anesthesia requiring intubation or ventilatory support) within 3 months prior to randomization.
11. Cardiopulmonary bypass or thoracotomy within 2 years prior to randomization.
12. Undergoing valvular repair or replacement during scheduled CABG surgery.
13. Chronic obstructive pulmonary disease (COPD) requiring oxygen therapy.
14. Decompensating congestive heart disease
15. Subjects on immunosuppressive drugs, such as azathioprine, chemotherapeutic agents, mycophenolate, monoclonal antibodies, or more than 20 mg/day prednisone, within the previous 3 months
16. Receipt of any investigational agent or device within 30 days of screening.

Primary outcomes:
measure: The primary objective of this study was to compare mild cognitive impairment in the AL-208 group with the placebo group at 14±3 days after coronary artery bypass graft (CABG) surgery.
timeFrame: 14 days
Secondary outcomes:
measure: The safety profile of AL-208 in subjects undergoing CABG surgery
timeFrame: 14 days
measure: The effect of treatment with AL-208 on postoperative personality changes in subjects undergoing CABG surgery
timeFrame: 14 days
measure: Concentration of AL-208 in plasma in subjects undergoing CABG surgery
timeFrame: 14 days
Other outcomes:
Locations:
city: Laguna Hills
country: United States
facility: Physicians Clinical Research Corp.
state: California
city: Sacramento
country: United States
facility: Sacramento Heart and Vascular Research Center
state: California
city: Jacksonville
country: United States
facility: Jacksonville Center for Clinical Research
state: Florida
city: South Miami
country: United States
facility: Miami Research Associates
state: Florida
city: Atlanta
country: United States
facility: Piedmont Hospital Research Institute
state: Georgia
city: Atlanta
country: United States
facility: The Atlanta Heart and Vascular Research Group
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Elk Grove Village
country: United States
facility: Chicago Heart Institute and Vein Clinic
state: Illinois
city: Hindsdale
country: United States
facility: Illinois Heart and Vascular Foundation
state: Illinois
city: Ft. Wayne
country: United States
facility: Indiana/Ohio Heart Cardiothoracic and Vascular Surgeons
state: Indiana
city: Boston
country: United States
facility: Brigham & Women's Hospital
state: Massachusetts
city: Flint
country: United States
facility: Cardiothoracic Associates
state: Michigan
city: New York
country: United States
facility: NYU Medical Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Raleigh
country: United States
facility: Carolina Cardiovascular Surgical Associates, PA
state: North Carolina
city: Wilmington
country: United States
facility: Memory Assessment and Research Services
state: North Carolina
city: Toledo
country: United States
facility: St. Vincent Mary Medical Center
state: Ohio
city: Tulsa
country: United States
facility: Tulsa Clinical Resesarch, LLC
state: Oklahoma
city: Erie
country: United States
facility: Consultants in Cardiovascular Diseases Inc.
state: Pennsylvania
city: Knoxville
country: United States
facility: Clinical Research Solutions, PC
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Dallas
country: United States
facility: Clinical Cardiovascular Research Center
state: Texas
city: Houston
country: United States
facility: St. Luke's Episcopal Hospital
state: Texas
city: Falls Church
country: United States
facility: Inova Fairfax Hospital
state: Virginia
city: Mechanicsville
country: United States
facility: Cardiac and Thoracic Surgical Associates, Ltd.
state: Virginia
city: Tacoma
country: United States
facility: Multicare Health Systems
state: Washington
city: London
country: Canada
facility: London health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
Study officials:
affiliation: Medical Monitor on behalf of Allon Therapeutics
name: Elena Matthews, MD
role: STUDY_DIRECTOR
References: