Study to Evaluate Safety, Tolerability, and Effect of AL208 on Mild Cognitive Impairment Following Coronary Artery Bypass Graft Surgery

Mild Cognitive Impairment Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00404014
• Other study ID #: AL 208-201
• Status: Completed
• Phase: Phase 2
• First received: November 24, 2006
• Last updated: October 18, 2012
• Start date: August 2006
• Est. completion date: June 2008

Study information

• Verified date: October 2012
• Source: Allon Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCanada: Health Canada
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 234
• Est. completion date: June 2008
• Est. primary completion date: June 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 50 Years to 79 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cognition Disorders
• Mild Cognitive Impairment

Intervention

Drug:
• AL-208
1 dose of 300 mg
• Placebo
1 dose of placebo

Locations

Country	Name	City	State
Canada	London health Sciences Centre	London	Ontario
Canada	Toronto General Hospital	Toronto	Ontario
United States	Piedmont Hospital Research Institute	Atlanta	Georgia
United States	The Atlanta Heart and Vascular Research Group	Atlanta	Georgia
United States	Brigham & Women's Hospital	Boston	Massachusetts
United States	Rush University Medical Center	Chicago	Illinois
United States	Clinical Cardiovascular Research Center	Dallas	Texas
United States	Duke University Medical Center	Durham	North Carolina
United States	Chicago Heart Institute and Vein Clinic	Elk Grove Village	Illinois
United States	Consultants in Cardiovascular Diseases Inc.	Erie	Pennsylvania
United States	Inova Fairfax Hospital	Falls Church	Virginia
United States	Cardiothoracic Associates	Flint	Michigan
United States	Indiana/Ohio Heart Cardiothoracic and Vascular Surgeons	Ft. Wayne	Indiana
United States	Illinois Heart and Vascular Foundation	Hindsdale	Illinois
United States	St. Luke's Episcopal Hospital	Houston	Texas
United States	Jacksonville Center for Clinical Research	Jacksonville	Florida
United States	Clinical Research Solutions, PC	Knoxville	Tennessee
United States	Physicians Clinical Research Corp.	Laguna Hills	California
United States	Cardiac and Thoracic Surgical Associates, Ltd.	Mechanicsville	Virginia
United States	Vanderbilt University	Nashville	Tennessee
United States	NYU Medical Center	New York	New York
United States	Carolina Cardiovascular Surgical Associates, PA	Raleigh	North Carolina
United States	Sacramento Heart and Vascular Research Center	Sacramento	California
United States	Miami Research Associates	South Miami	Florida
United States	Multicare Health Systems	Tacoma	Washington
United States	St. Vincent Mary Medical Center	Toledo	Ohio
United States	Tulsa Clinical Resesarch, LLC	Tulsa	Oklahoma
United States	Memory Assessment and Research Services	Wilmington	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Allon Therapeutics

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	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.	14 days	No
Secondary	The safety profile of AL-208 in subjects undergoing CABG surgery	The safety profile of AL-208 in subjects undergoing CABG surgery	14 days	Yes
Secondary	The effect of treatment with AL-208 on postoperative personality changes in subjects undergoing CABG surgery	The effect of treatment with AL-208 on postoperative personality changes in subjects undergoing CABG surgery	14 days	No
Secondary	Concentration of AL-208 in plasma in subjects undergoing CABG surgery	Concentration of AL-208 in plasma in subjects undergoing CABG surgery	14 days	No