Feasibility of a randomized controlled pilot study using propranolol to decrease beta-adrenergic signaling in hematopoietic stem cell transplant recipients

Abstract

Randomized controlled trials (RCTs) incorporating basic science psychoneuroimmunology (PNI) mechanisms into translatable clinical findings are critical to implementing PNI discoveries into standard medical practice. Biobehavioral pathways involving stress-induced beta-adrenergic signaling are implicated in tumor progression, with beta-blockers demonstrating efficacy in diminishing these effects in animals. We conducted a proof-of-concept RCT pilot study evaluating the feasibility of prophylactic beta-blocker administration with propranolol (peak dose 80 mg/day) to individuals undergoing a rigorous cancer treatment – autologous hematopoietic cell transplantation - for multiple myeloma. Twenty-two patients have been enrolled (target accrual = 25). 199 individuals completed screening between July 2015 and January 2017; 16 patients declined study participation and 28 enrolled in other oncology treatment trials. Of the remaining 155 patients, 132 were ineligible. The most common reason for ineligibility was current beta- blocker usage (44; 22% of total screened). Of the 23 eligible patients who did not decline or enroll in another trial, 22 were successfully enrolled in the propranolol trial (96%). One of the 11 patients in the treatment arm was unable to complete the propranolol course due to hypotension; > 90% of treatment arm patients were compliant with all 5 weeks of propranolol administration. In sum, adjunctive PNI pharmacologically-based cancer trials may compete for enrollment with primary oncology treatment trials, though enrollment is feasible and cancer patients undergoing rigorous antineoplastic treatment tolerate and are compliant with concurrent beta-blocker therapy.