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Pilot Study Using Propranolol to Decrease Gene Expression of Stress-Mediated Beta-Adrenergic Pathways in Hematopoietic Stem Cell Transplant Recipients

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ClinicalTrials.gov Identifier: NCT02420223
Recruitment Status : Active, not recruiting
First Posted : April 17, 2015
Last Update Posted : March 28, 2019
Sponsor:
Collaborator:
University of California, Los Angeles
Information provided by (Responsible Party):
Jennifer M. Knight, Medical College of Wisconsin

Tracking Information
First Submitted Date  ICMJE March 3, 2015
First Posted Date  ICMJE April 17, 2015
Last Update Posted Date March 28, 2019
Study Start Date  ICMJE August 2015
Actual Primary Completion Date July 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 6, 2016)
Change in beta-adrenergically mediated gene expression following beta-blocker administration [ Time Frame: Change assessed from pre-transplant (Day -7) to day of transplant (Day 0) and from day of transplant to 4 weeks post-transplant (Beta-blocker administration starts Day -7 and continues through 4 weeks post-transplant) ]
Original Primary Outcome Measures  ICMJE
 (submitted: April 16, 2015)
Change in beta-adrenergically mediated gene expression following beta-blocker administration [ Time Frame: Change assessed from pre-transplant (Day -21) to day of transplant (Day 0) and from day of transplant to 4 weeks post-transplant (Beta-blocker administration starts Day -21 and continues through 4 weeks post-transplant) ]
Change History Complete list of historical versions of study NCT02420223 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 16, 2015)
  • Change in depression and anxiety as a function of beta-blocker administration [ Time Frame: Differences between beta-blocker groups assessed at 4 weeks and 100 days after transplant ]
    Change will be assessed using the Hospital Anxiety and Depression Scale (HADS)
  • Incidence of engraftment syndrome as a function of beta-blocker administration [ Time Frame: Differences between beta-blocker groups assessed at 4 weeks and 100 days after transplant ]
  • Rates of neutrophil and platelet engraftment as a function of beta-blocker administration [ Time Frame: Differences between beta-blocker groups assessed at 4 weeks and 100 days after transplant ]
  • Incidence of infection as a function of beta-blocker administration [ Time Frame: Differences between beta-blocker groups assessed at 4 weeks and 100 days after transplant ]
  • Differences in myeloma response as a function of beta-blocker administration [ Time Frame: Differences between beta-blocker groups assessed at 4 weeks and 100 days after transplant ]
    The trial will assess the rates of very good partial response (VGPR) or better (near complete response (nCR), CR, and stringent CR (sCR)) according to the International Uniform Response Criteria at day 100 post-HCT.
  • Differences in treatment-related mortality as a function of beta-blocker administration [ Time Frame: Differences between beta-blocker groups assessed at 4 weeks and 100 days after transplant ]
  • Differences in progression-free survival as a function of beta-blocker administration [ Time Frame: Differences between beta-blocker groups assessed at 4 weeks and 100 days after transplant ]
  • Differences in overall survival as a function of beta-blocker administration [ Time Frame: Differences between beta-blocker groups assessed at 4 weeks and 100 days after transplant ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pilot Study Using Propranolol to Decrease Gene Expression of Stress-Mediated Beta-Adrenergic Pathways in Hematopoietic Stem Cell Transplant Recipients
Official Title  ICMJE Randomized Controlled Pilot Study Using Propranolol to Decrease Gene Expression of Stress-Mediated Beta-Adrenergic Pathways in Hematopoietic Stem Cell Transplant Recipients
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.
Detailed 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Condition  ICMJE Multiple Myeloma
Intervention  ICMJE Drug: Propranolol
Other Name: Hemangeol, Inderal LA, Inderal XL, InnoPran XL, Inderal
Study Arms  ICMJE
  • Experimental: Propranolol
    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.
    Intervention: Drug: Propranolol
  • No Intervention: Control Arm
    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.
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: December 18, 2017)
25
Original Estimated Enrollment  ICMJE
 (submitted: April 16, 2015)
40
Estimated Study Completion Date  ICMJE August 2019
Actual Primary Completion Date July 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 MCW 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02420223
Other Study ID Numbers  ICMJE PRO00024391
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Jennifer M. Knight, Medical College of Wisconsin
Study Sponsor  ICMJE Medical College of Wisconsin
Collaborators  ICMJE University of California, Los Angeles
Investigators  ICMJE
Principal Investigator: Jennifer Knight, MD Medical College of Wisconsin
PRS Account Medical College of Wisconsin
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP