Evaluation of the Safety and Efficacy of Ang-(1-7) to Enhance Cognitive Function in Participants Undergoing CABG

• Status: Suspended
• Trial end date: 2022-11-15
• Target enrollment: 0
• Participant gender: All

Summary

Coronary Artery Bypass Graft (CABG) is a surgical procedure known to be associated with cognitive impairment. Mechanisms of cognitive impairment are complex but may include insufficient oxygenation and inflammation due to exposure to the bypass circuit. Currently there are no approved therapeutics for the prevention or treatment of cognitive impairment in these patients.

A small peptide, Angiotensin-(1-7) [Ang-(1-7)], is known to decrease inflammation in the brain in animal models. Early studies in humans have shown it to be safe. This peptide is naturally produced by the body and has anti-inflammatory and vasodilatory effects. Investigators believe that Ang-(1-7) may be able to help lower the risk of cognitive dysfunction in patients undergoing CABG.

The goal of this project is to explore effects of the experimental peptide Angiotensin-(1-7) (Ang-(1-7) in patients undergoing an elective CABG surgery to determine its safety and efficacy to prevent cognitive dysfunction in patients undergoing CABG.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Arizona
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); National Institutes of Health (NIH); Suburban Hospital
• Treatments: Angiotensin I (1-7)

Criteria

Inclusion Criteria:

• Adult male or female first time cardiac surgical participants

• Elective on pump coronary artery bypass grafting (CABG)

• Age 60-80

• Signed, informed consent

• Geriatric Depression Scale score less than or = 14or Beck's Depression Inventory less than or = 20

• Score > or = 25 on the Mini-Mental State Examination (MMSE)

Exclusion Criteria:

• Recent (within 60 days) Cerebrovascular disease with neurological change

• Malignancy or pre-malignant state within 5 years not including non-melanoma skin cancer

• History of liver dysfunction with ongoing sequelae (including but not limited to liver enzymes > 2.5 x upper limit or normal (ULN) at screening).

• History of renal dysfunction with ongoing sequelae (including but not limited to creatinine value > 2.5 mg/dL at screening).

• Significant Lung Disease (FEV1< 1.5 L, pO2 <70 on room air, pCO2 >45)

• 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.

• Active substance abuse

• Less than Grade 7 education or inability to read and perform cognitive assessment.

• Significant neurological disorder affecting memory

• Uncontrolled atrial fibrillation prior to surgery

• Concurrent use of prescription medications specifically for memory enhancement including herbal or natural supplements

• General anesthesia (defined as anesthesia requiring intubation or ventilatory support) within 3 months prior to randomization.

• Cardiopulmonary bypass or thoracotomy within 2 years prior to randomization.

• Chronic obstructive pulmonary disease (COPD) requiring oxygen therapy.

• Participants on immunosuppressive drugs, such as azathioprine, chemotherapeutic agents, mycophenolate, monoclonal antibodies, or more than 20 mg/day prednisone, within the previous 3 months

• Receipt of any investigational agent or device within 30 days of screening

• MRI contraindication not limited to abnormally high weight or height to fit in scanner (Bore 70cm); Presence of device/hardware incompatible with MR imaging

• Conditions causing severe anemia

• Participant is practicing Jehovah Witness

• Sexually active males not practicing a medically acceptable method of contraception, unless there is documented azoospermia.