Carvedilol Failed to Improve Episodic Memory in Alzheimer’s Patients
Results from a pilot Phase 4 clinical trial evaluating the potential benefit of a known blood pressure and heart failure treatment, carvedilol, in Alzheimer’s disease showed the medicine had no effect in the episodic memory of patients. However, carvedilol was able to prevent the increase of beta-amyloid levels in cerebrospinal fluid.
Alzheimer’s disease is caused by abnormal and toxic accumulations of proteins, such as beta-amyloid and tau proteins, which interfere with the communication between nerve cells. Beta-amyloid peptide 42 (Abeta 42) is the most toxic form of beta-amyloid aggregates and is considered a primary driver for developing the disease.
Carvedilol, a beta-blocker, is an approved treatment for high blood pressure and heart failure. However, experiments in mouse models have suggested it interferes with the build-up of beta-amyloid aggregates in the brain, making it a potential therapy for Alzheimer’s disease.
A randomized placebo-controlled pilot Phase 4 trial (NCT01354444) evaluated the effectiveness and safety of carvedilol in patients with early-stage Alzheimer’s disease. Its primary goal was episodic memory (memory regarding personal facts and experiences) measured through the Hopkins Verbal Learning Test (HVLT). The secondary goal was the effect of carvedilol treatment in the levels of beta-amyloid in the cerebrospinal fluid.
Twenty-nine adult patients were enrolled at the trial site, the Johns Hopkins University School of Medicine in Baltimore, Maryland. Participants were randomized to receive either 25 mg/day of carvedilol (14 patients) or a placebo (15 patients), for six months. The carvedilol dose used in the trial was half of the maximum dose used in clinical practice.
The HVLT test was performed at the beginning of the trial, and after three and six months of treatment. Patients receiving carvedilol did not show an improvement in episodic memory (through HVLT scores), compared to participants on placebo.
However, when comparing beta-amyloid levels between the two groups of patients, some differences emerged. Cerebrospinal fluid samples were collected from six and 10 patients in the treatment and placebo group, respectively, at the beginning and at the end of the study.
While the mean levels of Abeta 42 in individuals receiving placebo showed a 25 percent increase after six months, patients receiving carvedilol had a slight reduction in Abeta 42 levels.
Although clinical effects were not observed, the data suggests that carvedilol might help prevent Alzheimer’s progression in terms of beta-amyloid accumulation.
Regarding safety, two severe adverse events (blood or neurologic problems) occurred in two patients. Most patients had non-severe adverse events, but none appeared to be related to treatment.
Due to the reduced number of participants and the slightly inconsistent results, further studies seem necessary to understand the potential of carvedilol for the treatment of Alzheimer’s disease.