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Pancreatic CancerPhase 2IMPULSNCT06145074

Examining Safety, Efficacy and Feasibility of Preoperative Propranolol in Patients With PDAC.

A Phase 2 study testing Propranolol in people with Pancreatic Cancer and Surgery, run by Zealand University Hospital at 2 sites in Denmark.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

The IMPULS trial is a randomized, triple-blinded, placebo controlled, single center, pilot trial examining the efficacy and safety of preoperative propranolol in patients scheduled for pancreatic cancer surgery. The study is conducted as a type 1 hybrid efficacy-implementation trial of 30 patients. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Pancreatic Cancer, Surgery
What is being tested?
Propranolol
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
30 participants
Where
2 sitesDenmark
Study dates
20 Mar 2024to 31 Dec 2035
Phase
Phase 2
Are there results?
Not yet: the study is under way

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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients with suspected surgically resectable pancreatic cancer
  • Indication for surgical treatment with curative intend.
  • Provide written informed consent.
  • Patients minimum 18 years old.
  • Women of childbearing potential (WOCBP) are defined as women ranging from the period of menarche till the post-menopausal period, unless permanently sterile (e.g., hysterectomy, bilateral salpingectomy and bilateral oophorectomy). Post-menopause is defined as no menses for 12 months without an alternative medical cause.
  • WOCBP should use a secure and highly effective birth control (as stated in the "Recommendations related to contraception and pregnancy testing in clinical trials", version 1.1., section 4.1, from the Clinical Trials Facilitation and Coordination Group) during the entire period of the trial. In cases of uncertainty regarding pregnancy, additional pregnancy testing either as highly sensitive serum or urine pregnancy test can be used.

Who cannot join

  • Patients with:
  • Chronic hypotension, systolic blood pressure < 100 mg Hg for women and < 110 mg Hg for men.
  • Bradycardia, pulse < 50 beats per minute.
  • Asthma or chronic obstructive lung disease
  • Heart insufficiency with affected (< 50 %) left ventricle ejection fraction (LVEF), treated or untreated.
  • Kidney insufficiency, defined as eGFR < 20 ml/min.
Show all 22Show fewer
  • Liver insufficiency defined as chronically high liver enzymes or known chronic liver disease (e.g., hepatitis, steatosis, cirrhosis).
  • Cor pulmonale
  • Cardiogenic shock
  • Severe peripheral circulatory disorders
  • Known or newly diagnosed current metabolic acidosis (e.g., in recent analysis of arterial puncture).
  • Known hypersensitivity to propranolol or to one or more of the excipients.
  • Currently untreated pheochromocytoma.
  • History of Prinzmetals angina.
  • History of sick sinus syndrome or atrioventricular block.
  • History of stroke or any previous cardiovascular event.
  • History of neoadjuvant oncological treatment for suspected primary pancreatic cancer.
  • Recent or present (within 3 months) use of propranolol or any other beta-blocker.
  • Recent or present (within 3 months) use of any of the following medications: anxiolytics, calcium channel blockers, beta-adrenergic receptor agonist.
  • Medical history that classifies the patient as frail or unsuitable for inclusion by the examining physician.
  • Histopathological examination revealing benign lesion.
  • Predictable poor compliance, due to pre-existing psychiatric disease, dementia or not able to read or speak sufficient Danish, resulting in not being able to provide a well-informed written consent.

Trial locations and contacts

2 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Ismail Gögenur, Professor contact

+4547323181

igo@regionsjaelland.dk

Adile Orhan, MD contact

+4560807762

aor@regionsjaelland.dk

Denmark2 sites, 2 recruiting
  • Department of Surgical Gastroenterology

    Copenhagen, 2200

    Stefan K Burgdorf, MD, PhD, +4535458225, stefan.kobbelgaard.burgdorf.02@regionh.dk

    Recruiting
  • Ismail Gögenur

    Køge, 4600

    Ismail Gögenur, Prof., +4547323181, igo@regionsjaelland.dk

    Adile Orhan, MD, +4560807762, aor@regionsjaelland.dk

    Not yet recruiting

Other trials in Denmark

About this study

Official title: Examining the Impact of Propranolol on Preoperative Anxiety and on Tumorigenic Changes in Patients With Pancreatic Ductal Adenocarcinomas: a Randomized, Triple-blinded, Placebo-controlled Pilot Trial

The IMPULS trial is a randomized, triple-blinded, placebo controlled, single center, pilot trial examining the efficacy and safety of preoperative propranolol in patients scheduled for pancreatic cancer surgery. The study is conducted as a type 1 hybrid efficacy-implementation trial of 30 patients.

This study is designed to provide pilot data for a future larger perioperative study of propranolol with the aim of improving outcomes for pancreatic cancer surgery.

Read more

In total, 30 participants will be allocated in a 1:1 ratio with 15 participants enrolled in each trial arm (propranolol vs. placebo). Participants will be allocated to either 40 mg propranolol twice daily or placebo twice daily in 10 days prior to planned surgery.

Primary outcomes: Evaluating the efficacy of preoperative propranolol on anxiety and in pro-tumorigenic changes (e.g., in the tumor tissue and in blood samples) in patients undergoing surgery for pancreatic cancer. Furthermore, to obtain follow up data (e.g., 90-day mortality, postoperative complications etc. on the patients receiving propranolol versus placebo). Heart rate variability among the participants will also be examined.

Secondary: Examining the safety and tolerability of 40 mg preoperative propranolol twice daily in patients undergoing surgery for pancreatic cancer.

Tertiary: Evaluating the feasibility and implementation of the trial (using the APEASE framework). This will help identify barriers and enablers to a future larger study.

Short-time propranolol treatment is considered safe with a mild and manageable safety-profile. Risk-management, mitigations and guidelines to ensure patient safety is included in the protocol. Since this clinical trial is exploratory in nature, no sample-size calculation is performed.

Read the detailed description

The study will be conducted as a pilot study to test efficacy, safety and feasibility of propranolol on preoperative anxiety in patients undergoing abdominal surgery for suspected pancreatic ductal adenocarcinoma (PDAC). Furthermore, the implementation of the trial including compliance of the participants in a hybrid type 1 setup will be examined.

A total of 30 participants will be included and randomized to receive either propranolol or placebo twice daily with 15 patients in each arm. Following this study, a power calculation will be done to reveal the actual number of needed participants in each arm for a potential follow-up randomized clinical trial on primary outcomes of interest. Thus, the results from this study can be used for future power calculations for clinical trials related to this topic.

Primary objectives: Efficacy

Evaluating the efficacy of preoperative propranolol on patient-experienced anxiety and on tumorigenic gene expression compared to placebo is the primary objective of this trial.

Primary objectives are further divided in to primary clinical objectives, primary translational objectives and exploratory endpoints.

Primary clinical objectives:

The primary clinical objectives are to evaluate preoperative patient-experienced anxiety in patients receiving the nonselective beta-2-adrenergic receptor inhibitor, propranolol, compared to placebo.

Further, heart rate variability (HRV) will be measured in order to evaluate changes in the autonomous nervous system in relation to surgery. HRV is calculated from the interval variation between consecutive R waves in an ECG time series and results suggest that it is associated with the intra- and postoperative complications. As HRV reflects sinoatrial node regulation, it is expected to be affected by the beta-adrenergic blockade caused by preoperative propranolol. Analyzing this relation will provide essential knowledge in understanding how HRV behaves perioperatively.

Lastly, follow up on the participants receiving propranolol compared to placebo will be done.

Primary clinical effect parameters:

The following primary effect parameters will be used to investigate the primary clinical objectives:

  • Anxiety levels will primarily be measured by The Hamilton Anxiety Rating Scale (HAM-A) and secondarily by The Hospital Anxiety and Depression Scale (HADS). The European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QoL) for pancreatic cancer will be used to assess quality of life.
  • HRV is calculated from continuous ECG gathered by a Holter monitor. The monitor is a small wearable apparatus with one lead, placed on the patient's sternum. It is applied on preoperative day 9 and will run continually until approximately postoperative day 7. The actual calculations are achieved post hoc using software specialized for HRV analysis.
  • Follow up at 30- and 90-days after surgery including parameters such as survival and postoperative complications.
  • Long-term follow up at as 1-year, 3- year and 5-year following surgery including survival and recurrence data.

Primary translational objectives:

The primary translational objectives are to examine the systemic (biochemical) and local changes (TME of resections) to propranolol treatment compared to placebo. Alterations in pro-metastatic and proinflammatory genes will specifically be analyzed.

Primary translational effect parameters:

  • Blood sampling for the analysis of pro-metastatic and proinflammatory biomarkers.
  • Expression of pro-metastatic and proinflammatory genes in formalin-fixed paraffin-embedded (FFPE) cancer tissue obtained after surgical resection.

Exploratory endpoints:

The potential influence of inter-participant genetic variations (pharmacogenetics) on measured levels of serum propranolol and response to surgical stress will be investigated as exploratory endpoints. The differences in drug metabolism (pharmacokinetics) among participants will also be of interest.

Secondary objectives: Safety

Secondarily, tolerance and safety of the intervention in this pilot study (e.g., adverse effects, number of patients that need dose reduction etc.) will be evaluated. Changes in heart rate (HR) and blood pressure (BP) during the intervention period will be examined to test safety and tolerability of preoperative propranolol.

Secondary effect parameters:

  • Measuring the changes in resting HR and BP during the intervention period with handed out blood pressure monitors.
  • Safety endpoints: light-headedness, lethargy, hypotension, bradycardia and other symptoms and side-effects that may be related to propranolol treatment.

Tertiary objectives: Feasibility

Additionally, the feasibility of this intervention using the APEASE framework, which assesses factors like affordability, practicability, effectiveness, acceptability, side-effects, and equity, thereby determining the willingness to adopt this strategy will be examined. This will help identify barriers and enablers to a future larger study. The details regarding the APEASE framework are described under assessments.

This trial will be conducted in accordance with the principles of Good Clinical Practice and reported according to the CONSORT and the complimentary StaRI standards for implementation studies.

Being tested
Propranolol, Placebo
Keywords
Propranolol, Beta-Blockers, PDAC, Pancreatic Cancer
Medical subject headings
Pancreatic Neoplasms

What participants receive

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

  • PropranololDrug

    Also called Inderal, Propal

    Oral administration.

  • PlaceboDrug

    Also called Inactive drug

    Oral administration.

Study groups in NCT06145074
Study groupRoleWhat they receive
PropranololExperimentalPropranolol will be administered 40 mg twice daily (morning and evening) in 10 days prior to surgery for pancreatic cancer
Receives: Drug: Propranolol
PlaceboPlacebo comparatorPlacebo will be administered twice daily (morning and evening) in 10 days prior to surgery for pancreatic cancer.
Receives: Drug: Placebo

What is being measured

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

  1. Preoperative anxiety

    Assessed through the Hamilton Anxiety Rating Scale (HAMA) questionnaire

    Measured: Obtained preoperatively at baseline (immediately after inclusion) and immediately after intervention (before surgery)

  2. Preoperative anxiety and depression

    Assessed through the Hospital Anxiety and Depression Scale (HADS) questionnaire

    Measured: Obtained preoperatively at baseline (immediately after inclusion) and immediately after intervention (before surgery)

  3. Preoperative quality of life

    Preoperative quality of life assessed through the quality of life questionnaire.

    Measured: Obtained preoperatively at baseline (immediately after inclusion) and immediately after intervention (before surgery)

  4. Density and subtypes of tumor-infiltrating lymphocytes in the tumor microenvironment.

    Histopathological assessment of the density and subtypes of tumor-infiltrating lymphocytes.

    Immunohistochemistry technique will be used.

    Measured: Through study completion. At latest within 1 year from last participant completes trial.

  5. Desmoplasia in the tumor microenvironment.

    Histopathological assessment of desmoplasia in the tumor microenvironment.

    Immunohistochemistry technique will be used.

    Measured: Through study completion. At latest within 1 year from last participant completes trial.

  6. Neural markers in the tumor microenvironment.

    Histopathological assessment of neural marker expression (e.g., NGF, BDNF, tyrosin hydroxylase)

    Immunohistochemistry technique will be used.

    Measured: Through study completion. At latest within 1 year from last participant completes trial.

  7. Adrenergic receptor (ADRB1&ADRB2) expression in the tumor microenvironment.

    Histopathological assessment of the expression of adrenergic receptors (ADRB1 and ADRB2).

    Immunohistochemistry technique will be used for this purpose.

    Measured: Through study completion. At latest within 1 year from last participant completes trial.

  8. Spatial distribution of immune cells in the tumor microenvironment.

    Spatial distribution of immune cells in the tumor microenvironment using Immunohistochemistry technique and NanoString GeoMx techniques will be used for this purpose.

    Measured: Through study completion. At latest within 1 year from last participant completes trial.

  9. Immune cells and subtypes in blood samples

    Assessing the number and subsets of immune cells in the obtained blood samples before and after propranolol treatment and between the two arms (propranolol versus placebo). This will be examined through FlowCytometry.

    Measured: Through study completion. At latest within 1 year from last participant completes trial.

  10. Circulating tumor cells before and after intervention in blood samples.

    Assessment of circulating tumor cells in blood samples before and after intervention.

    Measured: Through study completion. At latest within 1 year from last participant completes trial.

  11. RNA-level gene expression in blood samples.

    RNA-level expression of genes related to immune-surveillance through NanoString nCounter technique.

    Measured: Through study completion. At latest within 1 year from last participant completes trial.

  12. Heart rate variability in both trial arms

    Examining differences in heart rate variability among participants and between intervention and comparator group.

    Measured: Through study completion, an average of 1 year.

  13. Postoperative complications

    Assessment of postoperative complications based on the Clavien-Dindo Score (CD) ranging from I to V, where I is any decline from normal postoperative course and V is death of patient.

    Measured: After participant finishes trial and when last follow up (5 years from surgery) date is due.

  14. Survival 30-days after surgery

    Assessment of survival 30 days after surgery.

    Measured: After participant finishes trial and when last follow up (5 years from surgery) date is due.

  15. Survival 90-days after surgery

    Assessment of survival 90 days after surgery.

    Measured: After participant finishes trial and when last follow up (5 years from surgery) date is due.

  16. Overall survival 1-year after surgery

    Assessment of overall surival 1-year after surgery

    Measured: After participant finishes trial and when last follow up (5 years from surgery) date is due.

  17. Overall survival 3-years after surgery

    Assessment of overall survival 3-years after surgery

    Measured: After participant finishes trial and when last follow up (5 years from surgery) date is due.

  18. Overall survival 5-years after surgery

    Assessment of overall survival 5-years after surgery

    Measured: After participant finishes trial and when last follow up (5 years from surgery) date is due.

Secondary outcomes (2)
  1. Safety of 40 mg propranolol twice daily on blood pressure.

    Examining the safety of preoperative propranolol 40 mg twice daily prior to elective surgery for pancreatic cancer by continuous at-home measurements of blood pressure twice daily during the intervention period.

    Measured: Through study completion, within 14 days after surgery.

  2. Safety of 40 mg propranolol twice daily on heart rate.

    Examining the safety of preoperative propranolol 40 mg twice daily prior to elective surgery for pancreatic cancer by continuous at-home measurements of heart rate twice daily during the intervention period.

    Measured: Through study completion, within 14 days after surgery.

Timeline

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

  1. First posted22 Nov 2023
  2. Study start20 Mar 2024
  3. Primary completion31 Dec 2026 (estimated)
  4. Study completion31 Dec 2035 (estimated)

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
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
30 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06145074
Sponsor's protocol ID
EU CT 2023-506553-37-00
Acronym
IMPULS
Status last verified
Nov 2023
First submitted
8 Nov 2023
Last updated
28 Mar 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Propranolol in people with Pancreatic Cancer and Surgery, run by Zealand University Hospital at 2 sites in Denmark.

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 22 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: looking for participants now, as of the sponsor's last update on 28 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Denmark. 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. Some participants in this study may receive a placebo. 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?

This study is still under way. Results are not available in the source record yet.

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

Contact Ismail Gögenur, Professor (+4547323181, igo@regionsjaelland.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Preoperative anxiety (time frame: Obtained preoperatively at baseline (immediately after inclusion) and immediately after intervention (before surgery)). The study lists 18 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
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 28 Mar 2024.

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