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

NCT02420223 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: PRO00024391
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Multiple Myeloma

Keywords

Recipients

Outcome Measures

Primary Outcomes (1)

• Beta-adrenergically Mediated Gene Expression (Change From Baseline)

  Expression (up or down regulation) of genes involved in the stress response can be modulated through the beta-adrenergic pathway. The log2 RNA abundance is a means to normalize results to determine whether a gene is up regulated (value greater than 1) or down regulated (value less than 1). Differential change in log2 RNA abundance is defined by the fold change (FC) as log2FC=Log2(B)-Log2(A). Logarithmic measures are unitless. The change in the measure between two time points determines whether a gene has up-or down-regulated.

  Baseline (Pre-Transplant); 4 weeks post-transplant

Secondary Outcomes (6)

• Patient-reported Depression and Anxiety Scores

  Baseline and 4 weeks

• Number of Subjects Experiencing Engraftment Syndrome as a Function of Beta-blocker Administration

  4 weeks

• Time (Days) to Neutrophil Engraftment

  4 weeks after transplant

• Time (Days) to Platelet Engraftment

  4 weeks

• Number of Participants Diagnosed With Culture-positive Infection or Neutropenic Fever Greater Than 100.4 Degrees Fahrenheit

  Up to 100 days after transplant

Study Arms (2)

Propranolol

EXPERIMENTAL

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.

Drug: Propranolol

Control Arm

NO INTERVENTION

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.

Interventions

Propranolol DRUG

Also known as: Hemangeol, Inderal LA, Inderal XL, InnoPran XL, Inderal

Propranolol

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with multiple myeloma receiving an autologous HCT are eligible when the following criteria are met:
• years of age
• ≤ 1 year since initiation of systemic anti-myeloma therapy
• Patient is scheduled for autologous hematopoietic stem cell transplant as the upfront therapy for their multiple myeloma
• Karnofsky Performance Status of ≥90 %; patients eligible for HCT are eligible for the study
• All men and women must agree to practice effective contraception during the study period if not otherwise documented to be infertile.

You may not qualify if:

• Prior autologous HCT
• Non secretory multiple myeloma
• Concurrent beta-blocker therapy at or within 3 weeks of study entry.
• Previous intolerance to beta-blocker therapy
• 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
• 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)
• Concurrent use of medications as specified in the protocol throughout the study or within one week of study entry.
• Pregnant or lactating women

Sponsors & Collaborators

• Medical College of Wisconsin: lead
• University of California, Los Angeles: collaborator

Study Sites (1)

Froedtert Hospital and the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (2)

• Knight JM, Rizzo JD, Hari P, Pasquini MC, Giles KE, D'Souza A, Logan BR, Hamadani M, Chhabra S, Dhakal B, Shah N, Sriram D, Horowitz MM, Cole SW. Propranolol inhibits molecular risk markers in HCT recipients: a phase 2 randomized controlled biomarker trial. Blood Adv. 2020 Feb 11;4(3):467-476. doi: 10.1182/bloodadvances.2019000765.

  PMID: 32027744 RESULT

• Knight JM, Kerswill SA, Hari P, Cole SW, Logan BR, D'Souza A, Shah NN, Horowitz MM, Stolley MR, Sloan EK, Giles KE, Costanzo ES, Hamadani M, Chhabra S, Dhakal B, Rizzo JD. Repurposing existing medications as cancer therapy: design and feasibility of a randomized pilot investigating propranolol administration in patients receiving hematopoietic cell transplantation. BMC Cancer. 2018 May 24;18(1):593. doi: 10.1186/s12885-018-4509-0.

  PMID: 29793446 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Propranolol; propranolol CR

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds

Results Point of Contact

• Title: Dr. Jennifer Knight
• Organization: Medical College of Wisconsin

jknight@mcw.edu

866-680-0505

Study Officials

• Jennifer Knight, MD

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: March 3, 2015
• First Posted: April 17, 2015
• Study Start: July 17, 2015
• Primary Completion: July 1, 2018
• Study Completion: February 1, 2020
• Last Updated: June 7, 2021
• Results First Posted: June 7, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)