Safety, Tolerability, and Feasibility of Young Plasma Infusion in the Plasma for Alzheimer Symptom Amelioration Study: A Randomized Clinical Trial.

Importance: Young mouse plasma restores memory in aged mice, but, to our knowledge, the effects are unknown in patients with Alzheimer disease (AD). Objective: To assess the safety, tolerability, and feasibility of infusions of young fresh frozen plasma (yFFP) from donors age 18 to 30 years in patients with AD. Design, Setting, and Participants: The Plasma for Alzheimer Symptom Amelioration (PLASMA) study randomized 9 patients under a double-blind crossover protocol to receive 4 once-weekly infusions of either 1 unit (approximately 250 mL) of yFFP from male donors or 250 mL of saline, followed by a 6-week washout and crossover to 4 once-weekly infusions of an alternate treatment. Patients and informants were masked to treatment and subjective measurements. After an open-label amendment, 9 patients received 4 weekly yFFP infusions only and their subjective measurements were unmasked. Patients were enrolled solely at Stanford University, a tertiary academic medical center, from September 2014 to December 2016, when enrollment reached its target. Eighteen consecutive patients with probable mild to moderate AD dementia, a Mini-Mental State Examination (score of 12 to 24 inclusive), and an age of 50 to 90 years were enrolled. Thirty-one patients were screened and 13 were excluded: 11 failed the inclusion criteria and 2 declined to participate. Interventions: One unit of yFFP from male donors/placebo infused once weekly for 4 weeks. Main Outcome and Measures: The primary outcomes were the safety, tolerability, and feasibility of 4 weekly yFFP infusions. Safety end point analyses included all patients who received the study drug/placebo. Results: There was no difference in the age (mean [SD], 74.17 [7.96] years), sex (12 women [67%]), or baseline Mini-Mental State Examination score (mean [SD], 19.39 [3.24]) between the crossover (n = 9) and open-label groups (n = 9). There were no related serious adverse events. One patient discontinued participation because of urticaria and another because of an unrelated stroke. There was no statistically significant difference between the plasma (17 [94.4%]) and placebo (9 [100.0%]) cohorts for other adverse events, which were mild to moderate in severity. The most common adverse events in the plasma group included hypertension (3 [16.7%]), dizziness (2 [11.1%]), sinus bradycardia (3 [16.7%]), headache (3 [16.7%]), and sinus tachycardia (3 [16.7%]). The mean visit adherence (n = 18) was 86% (interquartile range, 87%-100%) and adherence, accounting for a reduction in the total visit requirement due to early patient discontinuation, was 96% (interquartile range, 89%-100%). Conclusions and Relevance: The yFFP treatment was safe, well tolerated, and feasible. The study's limitations were the small sample size, short duration, and change in study design. The results warrant further exploration in larger, double-blinded placebo-controlled clinical trials. Trial Registration: ClinicalTrials.gov Identifier: NCT02256306.

Topical alprostadil (PGE1) for the treatment of female sexual arousal disorder: in-clinic evaluation of safety and efficacy.

This multi-center, randomized, placebo-controlled, crossover design study evaluated the effects of a topical alprostadil solution for the treatment of female sexual arousal disorder (FSAD). A total of 79 naturally or surgically post menopausal women with FSAD were treated with either 100 or 400 micrograms of alprostadil solution and placebo, delivered on separate clinic visits in random order. Study drug was applied to the external genitalia and was followed by 30 minutes of visual sexual stimulation. Study evaluations included investigator assessments of genital vasocongestion and patient assessments of physical and emotional sexual arousal, and sexual satisfaction. Genital vasocongestion in response to PGE1 was significantly greater than placebo (p < 0.0001) at each dose level and at all post dosing time points. Patient assessments of physical and emotional arousal and sexual satisfaction were significantly greater than placebo with the 400 mcg dose, but not with the 100 mcg dose of alprostadil. Topical alprostadil was well tolerated with no reports of significant systemic side effects. The most common adverse event was mild, transient genital burning typically < 1 minute duration. Other side effects were mild-moderate, resolving within two hours of application. These data suggest topical alprostadil should be further researched as a potentially appropriate on-demand therapeutic choice for women experiencing FSAD.