Study of Propranolol to Decrease Gene Expression of Stress-Mediated Beta-Adrenergic Pathways in HCT Recipients

Medical College of Wisconsin

Status and phase: Completed; Phase 2

Conditions: Multiple Myeloma

Treatments: Drug: Propranolol

Study type: Interventional

Funder types: Other

Identifiers

NCT02420223

PRO00024391

Details and patient eligibility

About

This is a randomized controlled pilot study designed to evaluate whether the beta-adrenergic antagonist propranolol is effective in decreasing gene expression of stress-mediated beta-adrenergic pathways among a cohort of individuals receiving an autologous hematopoietic stem cell transplant (HCT) for multiple myeloma.

Full description

This is a randomized controlled pilot study designed to evaluate whether a drug designed to block the physiologic effects of stress is effective at blocking stress-related gene expression in people receiving autologous stem cell transplants (their own cells) for multiple myeloma. Such stress-related gene expression is one way that the body is programmed to make specific proteins under conditions of stress. These proteins are believed to contribute to worse health outcomes. By using the drug propranolol, we aim to see whether we might block these negative health effects of stress as occur in the cancer setting and during the transplant process. We hypothesize that individuals taking propranolol will have more favorable gene expression.

We will enroll 40 individuals, randomizing half to receive propranolol and half to serve as the control group not on the study drug. Study participants will start propranolol three weeks prior to their transplant and continue it until 30 days after the transplant. We will explore the effect of socioeconomic status, depression, and anxiety on individuals' gene expression response to propranolol with the idea that the more impoverished, anxious, or depressed individuals will display an even greater change in their gene expression. Part of the purpose of this study is also be to assess whether it is feasible to give this drug to individuals with cancer. Results of this study may inform larger trials assessing the effects of propranolol on cancer progression.

Enrollment: 25 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Patients with multiple myeloma receiving an autologous HCT are eligible when the following criteria are met:

1. 18-75 years of age
2. ≤ 1 year since initiation of systemic anti-myeloma therapy
3. Patient is scheduled for autologous hematopoietic stem cell transplant as the upfront therapy for their multiple myeloma
4. Karnofsky Performance Status of ≥90 %; patients eligible for HCT are eligible for the study
5. All men and women must agree to practice effective contraception during the study period if not otherwise documented to be infertile.

Exclusion criteria

1. Prior autologous HCT
2. Non secretory multiple myeloma
3. Concurrent beta-blocker therapy at or within 3 weeks of study entry.
4. Previous intolerance to beta-blocker therapy
5. Any medical contraindications to beta-blocker therapy including, but not limited to, symptomatic hypotension; drug hypersensitivity; sinus bradycardia, sick sinus syndrome, or 2nd or 3rd degree atrioventricular block without a pacemaker; uncompensated heart failure; or uncontrolled asthma
6. Active, untreated depression screened for by the HCT physician (Patients who screen positive will be offered a referral to the Medical College of Wisconsin Psycho-Oncology program for further evaluation and treatment)
7. Concurrent use of medications as specified in the protocol throughout the study or within one week of study entry.
8. Pregnant or lactating women

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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25 participants in 2 patient groups

Propranolol

Experimental group

Description:

Patient's randomized to the Propranolol arm will be starting 7 days prior to transplant and continuing through 28 days post-transplant. Propranolol will start at 20mg twice daily and will be titrated to 40mg twice daily as tolerated. Both groups will come back to the hospital weekly in order to assess items such as patient's level of anxiety, depression, your adherence, and also to monitor for side effects. The patient's will complete questionnaires during your visit. These will take approximately 15 minutes to complete. This will continue for up to 7 total weeks for patient's on the Propranolol arm.

Treatment:

Drug: Propranolol

Control Arm

No Intervention group

Description:

Both groups will come back to the hospital weekly in order to assess items such as patient's level of anxiety, depression, your adherence, and also to monitor for side effects. The patient's will complete questionnaires during your visit. These will take approximately 15 minutes to complete. This will continue for 6 total weeks for patient's on the control arm.