A Multicenter Randomized Controlled Trial To Evaluate the Efficacy and Safety of Nelfinavir in Patients with Mild COVID-19.

Nelfinavir, an orally administered inhibitor of human immunodeficiency virus protease, inhibits the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) . We conducted a randomized controlled trial to evaluate the clinical efficacy and safety of nelfinavir in patients with SARS-CoV-2 infection. We included unvaccinated asymptomatic or mildly symptomatic adult patients who tested positive for SARS-CoV-2 infection within 3 days before enrollment.

Efficacy and safety of nelfinavir in asymptomatic and mild COVID-19 patients: a structured summary of a study protocol for a multicenter, randomized controlled trial.

Objectives: The aim of this trial is to evaluate the antiviral efficacy, clinical efficacy, and safety of nelfinavir in patients with asymptomatic and mild COVID-19.

Trial Design: The study is designed as a multicenter, open-label, blinded outcome assessment, parallel group, investigator-initiated, exploratory, randomized (1:1 ratio) controlled clinical trial.

Participants: Asymptomatic and mild COVID-19 patients will be enrolled in 10 university and teaching hospitals in Japan.

An open-label continuation trial of sirolimus for tocilizumab-refractory idiopathic multicentric Castleman disease: Study protocol for an investigator-initiated, multicenter, open-label trial (SPIRIT compliant).

Background: Interleukin 6 (IL-6) inhibitors are the first-line treatment for idiopathic multicentric Castleman disease (iMCD); however, there is no established treatment for cases that are resistant to IL-6 inhibitors. Although sirolimus, a mammalian target of rapamycin inhibitor, has been suggested to be effective in patients with iMCD, the long-term safety and efficacy of sirolimus on individuals with IL-6 inhibitor-resistant iMCD have not been evaluated.

Methods/design: In this investigator-initiated, multicenter, open-label trial, the long-term safety of sirolimus will be evaluated in patients participating in a placebo-controlled, randomized, double-blind, parallel-group trial on tocilizumab (TCZ)-resistant iMCD.

Randomized, double-blind, placebo-controlled, parallel-group trial of sirolimus for tocilizumab-resistant idiopathic multicentric Castleman disease: Study protocol for clinical trial.

Background: Idiopathic multicentric Castleman disease (iMCD) is a rare lymphoproliferative disorder of unknown etiology with systemic symptoms that include fever, night sweats, weight loss, and fatigue. Although tocilizumab (TCZ), which is a recombinant, humanized, anti-human interleukin 6 receptor monoclonal antibody, has been recommended to treat patients with iMCD, 40% of patients with iMCD do not achieve complete remission with TCZ treatment.

Methods/design: In this phase II, investigator-initiated, multicenter, double-blind, randomized, parallel-group trial, the efficacy and safety of sirolimus will be compared with placebo in patients with TCZ-resistant iMCD.

Retinoic acid receptor stimulation protects midbrain dopaminergic neurons from inflammatory degeneration via BDNF-mediated signaling.

Functions of retinoic acid receptors (RARs) in adult CNS have been poorly characterized. Here we investigated potential neuroprotective action of tamibarotene (Am80), an RARalpha/beta agonist available for the treatment of acute promyelocytic leukemia, on midbrain dopaminergic neurons. Am80 protected dopaminergic neurons in rat midbrain slice culture from injury mediated by lipopolysaccharide-activated microglia, without affecting production of nitric oxide, a key mediator of cell injury.