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Multiple MyelomaPhase 2NCT02420223

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

A Phase 2 study testing Propranolol in people with Multiple Myeloma, run by Medical College of Wisconsin at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Multiple Myeloma
What is being tested?
Propranolol
Could I receive a placebo?
No, everyone receives an active treatment
How many people
25 participants
Where
1 siteUnited States
Study dates
17 Jul 2015to Feb 2020
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients with multiple myeloma receiving an autologous HCT are eligible when the following criteria are met:
  • 18-75 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.

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Froedtert Hospital and the Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

Other trials in United States

About this study

Official title: Randomized Controlled Pilot Study Using Propranolol to Decrease Gene Expression of Stress-Mediated Beta-Adrenergic Pathways in Hematopoietic Stem Cell Transplant (HCT) Recipients

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.

Read the 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.

Being tested
Propranolol
Keywords
Recipients
Medical subject headings
Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PropranololDrug

    Also called Hemangeol, Inderal LA, Inderal XL, InnoPran XL, Inderal

Study groups in NCT02420223
Study groupRoleWhat they receive
PropranololExperimentalPatient'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.
Receives: Drug: Propranolol
Control ArmNo interventionBoth 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.

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (6)

  1. Patient-reported Depression and Anxiety Scores

    This measure will be assessed using the Hospital Anxiety and Depression Scale (HADS). The HADS scale includes fourteen 4-response Likert-scale questions graded 0 to 3. Seven questions are specific to depression; 7 questions are specific to anxiety. The score is the total of the responses in their respective categories. Lower scores indicated less depression and/or anxiety. Scores 0-7 indicate normal status; scores 8-10 suggest borderline abnormal status; and scores 11-21 indicate abnormal status. Only anxiety scores are presented.

    Measured: Baseline and 4 weeks

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

    Number of subjects experiencing any of: fever, diarrhea or rash requiring steroid intervention within 48 hours before or after neutrophil recovery.

    Measured: 4 weeks

  3. Time (Days) to Neutrophil Engraftment

    This measure is the mean time to the beginning of three consecutive days where the neutrophil count (absolute neutrophil count) was 500 cells/mm^3 (0.5 x 10^9/L) or greater.

    Measured: 4 weeks after transplant

  4. Time (Days) to Platelet Engraftment

    This measure is the mean time to the beginning of three consecutive days where the platelet count is at least 20,000/mm^3 (20 x 10^9/L) unsupported by a platelet transfusion.

    Measured: 4 weeks

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

    This measure is the number of subjects diagnosed with culture-positive infection or neutropenic fever greater than 100.4 degrees Fahrenheit.

    Measured: Up to 100 days after transplant

  6. Number of Participants With Myeloma Response as a Function of Beta-blocker Administration

    This measure is the number of participants experiencing a response defined by the International Uniform Response Criteria as: very good partial response (VGPR) or better (near complete response (nCR), complete response (CR), and stringent CR (sCR) according to at day 100 post-Hematopoietic Cell Transplant.

    Measured: 100 days after transplant

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Apr 2015 (estimated)
  2. Study start17 Jul 2015
  3. Primary completionJul 2018
  4. Study completionFeb 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Supportive care
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
25 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02420223
Sponsor's protocol ID
PRO00024391
Status last verified
May 2021
First submitted
3 Mar 2015
Last updated
7 Jun 2021
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 32027744

  • 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.

    PubMed 29793446

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Propranolol in people with Multiple Myeloma, run by Medical College of Wisconsin at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Jun 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Beta-adrenergically Mediated Gene Expression (Change From Baseline) (time frame: Baseline (Pre-Transplant); 4 weeks post-transplant). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02420223, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jun 2021.

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