Rationale: The first clinical trial to evaluate the safety and tolerability of allopregnanolone (Allo), a naturally occurring brain steroid, in mild cognitive impairment and Alzheimers disease participants. Allo is an investigational drug molecule shown in animal studies to stimulate the birth of new neurons, rescue cognition and lower indicators of Alzheimers disease. Objectives: 1) The first group of participants in the trial will be given one dose of Allo once per week for 12 weeks, only increasing the dose for the next group of participants when the lower dose has been shown to be safe. The primary goal is to determine the highest dose that is safe and tolerated by participants. 2) Analysis will also be done on blood samples taken from participants at the beginning and end of the trial to determine how the body responds to the drug molecule. 3) As per FDA requirements, the trial will investigate potential safety concerns including blood vessel changes via brain imaging. Secondary goals are to assess the short-term effects of Allo treatment on learning and memory as well as detect changes via MRI brain imaging to help researchers prepare for a larger-scale clinical trial. Study Population: The trial will enroll 24 participants (12 post-menopausal women, 12 men) diagnosed with mild cognitive impairment (MCI) or early Alzheimers disease. Participants must be 55 years of age or older, have a score on the Mini-Mental State Examination greater than 20, and be able to provide informed consent. Study Methodology: Participants will be given Allo or placebo intravenously once per week for 12 weeks. Description of Study Arms: Each dose (low to high) will have a separate, gender balanced group of 8 participants. 6 participants will be given Allo and 2 will be given placebo. At the end of the study, 18 participants will have received Allo and 6 will have received placebo. Endpoints: To determine the safety and tolerability of Allo, the trial will evaluate 1) if any, how much sedation after each dose of Allo; 2) if any, how many side-effects participants report; 3) any clinically significant changes in participants (for example: blood tests, weight, heart rate, heart monitor, brain scan, tests of memory) and 4) changes in brain imaging.
Phase 1 - a new treatment that has not been tested, and researchers are looking for the best way to administer the treatment and how much can be given safely. Phase I trials are usually offered only to patients with advanced disease who would not be helped by other known treatments. Some patients are helped by these treatments, although in this early stage physicians don’t really know if the treatment will be effective.