Pulmonary HypertensionPhase 2PB-02NCT02216279
Phase-II Study of the Use of PulmoBind for Molecular Imaging of Pulmonary Hypertension
A Phase 2 study testing PulmoBind in people with Pulmonary Hypertension, run by Montreal Heart Institute at 3 sites in Canada.
Trial summary
Pulmonary hypertension or elevation of the pressure in the pulmonary vessels, results from various clinical conditions. It may be idiopathic (of unknown cause) or associated with numerous diseases including cardiovascular and lung disorders. Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Pulmonary Hypertension
- What is being tested?
- PulmoBind
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 3 sitesCanada
- Study dates
- Sep 2014to Sep 2015
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Male of female participants greater than 18 years of age,
- Female participants must be post-menopausal (defined as two year after last menstrual cycle) or surgically sterilized or use 1 form of contraception with a urine negative pregnancy test (commercial brand: first response kit) within 2 hours of study drug injection,
- Baseline measurements must be within limits of normal or judged non-clinically significant by the investigator:
- Blood pressure systolic 90 mmHg to 140 mmHg,and diastolic 50 mmHg to 90 mmHg;
- Heart rate: 50 to 100 beats per minute;
- Oral temperature: less than 37.6C;
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- Respiratory rate: 12 to 20 breaths per minute;
- Lung function testing within 6 months;
- Electrocardiogram in the past three years;
- Chest X-Ray in the past three years;
- Electrocardiogram.
- Male of female participants greater than 18 years of age and upper age 70,
- Female participants must be post-menopausal (defined as two year after last menstrual cycle) or surgically sterilized or use 1 form of contraception with a urine negative pregnancy test (commercial brand: first response kit) within 2 hours of study drug injection,
- Diagnosis of pulmonary hypertension (PH) according to the Dana Point PH classification of the following types:
- Type I: idiopathic, heritable or scleroderma spectrum of disease,
- Type IV: unoperated chronic thromboembolic PH.
- Participants with chronic thromboembolic pulmonary hypertension (CTEPH) must have a previous positive V/Q scan and multiple chronic/organised occlusive thrombi/emboli in the pulmonary arteries (main, lobar, segmental, subsegmental) on CT angiogram or conventional pulmonary angiography,
- Documented hemodynamic diagnosis of significant PH by right heart catheterization - performed at any time prior to Screening showing:
- Resting mean pulmonary arterial pressure (mPAP) > 25 mmHg and
- Resting pulmonary vascular resistance (PVR) > 240 dyn/s.cm5 and
- Resting capillary wedge pressure (PCWP) or left ventricular end diastolic pressure (LVDEP) ≤ 15 mmHg (if available),
- New York Heart Association (NYHA) functional class II-III,
- Six minutes walking distance test of ≥ 250 meters, and ≤ 450 meters within 6 months,
- Echocardiogram documented in the participants medical history (including an agitated saline study),
- Computed tomography of the chest documented in the participants medical history.
Who cannot join
- Any known chronic or acute medical condition with or without the need for chronic pharmacologic therapy or any condition that may interfere with normal biodistribution of PulmoBind. This includes but is not restricted to: lung parenchymal or lung vascular diseases such as chronic obstructive pulmonary disease, bronchitis, lung cancer, pleural effusion, emphysema, asthma, pulmonary fibrosis, occupational lung disease,pulmonary hypertension (primary or secondary), systemic hypertension, diabetes, cancer, kidney disease, liver disease, heart failure or previous myocardial infarction, coronary artery disease, peripheral vascular disease or inflammatory disease,
- Participants requiring chronic administration of any substance for a medical condition,
- Active smoking or history of smoking within 6 months,
- Alcoholism or known substance abuse,
- Psychotic,addictive or other disorder limiting the ability to provide informed consent or to comply with study requirements,
- Unable to tolerate study procedures (e.g. venipuncture, movement restrictions during imaging),
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- Previous nuclear medicine study within one week (to avoid cross-contamination).
- PULMONARY HYPERTENSION PARTICIPANTS:
- Participants with impaired renal function defined as estimated creatinine clearance ≤ 30 ml/min (eGFR with modification of diet in renal disease (MDRD) calculator formula),
- Significant liver impairment:
- Aspartate alanine transferase ( ALT) and/or Aspartate transaminase (AST) ≥ 3 x upper limit of normal (ULN)
- Bilirubin ≥ 1.5x ULN ( > 35% direct bilirubin)
- Unstable pulmonary arterial hypertension defined as recent syncope or World Health Organization (WHO) functional class IV,
- Participants with CTEPH not on anticoagulant therapy,
- Echocardiographic restrictive lung disease (total lung capacity < 70% of predicted) or obstructive (FEC1/Forced Vital Capacity < 70%),
- Systemic blood pressure < 90 mmHG systolic or less than 50 mmHG diastolic,
- Patient foramen ovale with significant right to left shunting with hypoxia (room air saturation < 88%),
- Active smoking within six months,
- More than minimal pulmonary fibrosis on high resolution computed tomography of the chest,
- The subject's clinical condition is such that they are not expected to remain clinically stable for the duration of the study,
- Active coronary artery disease or stable coronary artery disease that has required an intervention or any change of therapy within 6 months,
- Alcoholism or known substance abuse,
- Psychotic,addictive or other disorder limiting the ability to provide informed consent or to comply with study requirements,
- Participants who have participated in a clinical study involving another investigational drug or devise within four weeks before screening,
- Female participants who are pregnant or breastfeeding,
- Previous nuclear medicine study within one week,
- Unable to tolerate study procedures (e.g. venipuncture, movement restrictions during imaging).
Trial locations and contacts
3 sites in 1 country.
Canada3 sites
Montreal Heart Institute
Montreal, Quebec, H1T 1C8
Sir Mortimer B.Davis Jewish General Hospital
Montreal, Quebec
Institut Universitaire de Cardiologie et de Pneumologie de Quebec
Québec, Quebec
About this study
Pulmonary hypertension or elevation of the pressure in the pulmonary vessels, results from various clinical conditions. It may be idiopathic (of unknown cause) or associated with numerous diseases including cardiovascular and lung disorders. Affected individuals suffer from progressive shortness of breath and, in its most sever forms; pulmonary hypertension carries a worse prognosis than many types of cancer. There is no test currently that can easily and non-invasively detect abnormalities of the pulmonary circulation. Presently there is no cure for pulmonary hypertension and substantial research efforts are dedicated to the development of new drugs that will stop progression or better yet, reverse the disease process. The investigators do not know if any of the drugs currently commercialized for pulmonary hypertension directly improve the status of the pulmonary vessels since no test currently provides this information. Direct earlier detection of lung vessel abnormalities associated with pulmonary hypertension using a sensitive and non-invasive test would allow not only earlier testing of these and of new drugs, but would provide a much better surrogate of disease severity allowing more efficient pre-clinical drug testing. The aim of this phase II study is to evaluate the safety of PulmoBind in participants with pulmonary hypertension and its potential to detect abnormal pulmonary circulation associated within pulmonary hypertension.
Read the detailed description
Currently there is only one radiopharmaceutical agent approved in Canada (and the world) for clinical imaging of the pulmonary circulation, metastable isotope 99 of technetium. This agent is exclusively used for the diagnosis of physical defects of the circulation due to pulmonary embolus. There is imperative need for new lung tracers that will provide a greater safety profile while enabling functional as well as anatomical imaging of the pulmonary circulation. A novel adrenomedullin derivative has been developed, for molecular imaging of the pulmonary circulation. PulmoBind is labelled with metastable isotope 99 of technetium, the most commonly used imaging isotope in clinical nuclear medicine. PulmoBind is a adrenomedullin derivative specifically designed to bind to the adrenomedullin receptor while avoiding any hemodynamic effects. This novel tracer has the potential to help in the diagnosis and follow-up of various disorders of the pulmonary circulation for which there is currently no alternative. In PulmoBind I three escalating doses were administered and safety was assessed. The product was well tolerated and there were no safety concerns. Imaging revealed predominant lung uptake.
- Conditions
- Pulmonary Hypertension
- Being tested
- PulmoBind
- Keywords
- Pulmonary, Hypertension, PH, PulmoBind, Imaging
- Medical subject headings
- Hypertension, Pulmonary, Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PulmoBindDrug
PulmoBind is a peptide derived from human adrenomedullin (hAM1-52), labelled with 99mTc (imaging isotope used in clinical medicine).
| Study group | Role | What they receive |
|---|---|---|
| Pulmonary Hypertension Patients | Experimental | PulmoBind is a peptide derived from human adrenomedullin (hAM1-52), labelled with 99mTc (imaging isotope used in clinical medicine). Receives: Drug: PulmoBind |
| Control Non-Smoking Participants | Active comparator | PulmoBind is a peptide derived from human adrenomedullin (hAM1-52), labelled with 99mTc (imaging isotope used in clinical medicine). Receives: Drug: PulmoBind |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the absence of allergic reaction after repeated exposures to PulmoBind in healthy participants
Measured: Static lung uptake 10 minutes duration post injection
To determine the safety of PulmoBind in participants diagnosed with pulmonary hypertension.
Measured: Static lung uptake 10 minutes duration post injection
To determine the capacity of PulmoBind lung scan for the detection of abnormal pulmonary circulation associated with pulmonary hypertension.
This is an efficacy outcome
Measured: Status lung uptake 10 minutes duration post injection
Secondary outcomes (3)
To determine the intra-subject variability for quantification of PulmoBind lung uptake in control participants
Measured: Status lung uptake 10 minutes duration post injection
Determine the capacity of PulmoBind lung scan to diagnose pulmonary perfusion defects in participants with chronic thromboembolic pulmonary hypertension.
Measured: Status lung uptake 10 minutes duration post injection
To correlate lung PulmoBind scan results with parameters of the severity of pulmonary hypertension: 6 minutes walking distance, New York Heart Association functional class, pulmonary artery pressure measured by echo, pulmonary artery pressure measured by
Measured: Status lung uptake 10 minutes duration post injection
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Aug 2014 (estimated)
- Study startSep 2014
- Primary completionSep 2015
- Study completionSep 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pulmonary HypertensionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- Montreal Heart Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jocelyn Dupuis, MD, Principal investigator, Montreal Heart Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02216279
- Sponsor's protocol ID
- PulmoBind II safety Trial
- Acronym
- PB-02
- Status last verified
- Sep 2015
- First submitted
- 27 Jun 2014
- Last updated
- 30 Sep 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Harel F, Langleben D, Provencher S, Fournier A, Finnerty V, Nguyen QT, Letourneau M, Levac X, Abikhzer G, Guimond J, Mansour A, Guertin MC, Dupuis J. Molecular imaging of the human pulmonary vascular endothelium in pulmonary hypertension: a phase II safety and proof of principle trial. Eur J Nucl Med Mol Imaging. 2017 Jul;44(7):1136-1144. doi: 10.1007/s00259-017-3655-y. Epub 2017 Feb 24.
PubMed 28236024
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase-II Study of the Use of PulmoBind for Molecular Imaging of Pulmonary Hypertension
- ClinicalTrials.gov ID
- NCT02216279
- Acronym / sponsor ID
- PB-02 / PulmoBind II safety Trial
- Conditions
- Pulmonary Hypertension
- Keywords
- Pulmonary, Hypertension, PH, PulmoBind, Imaging
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- Montreal Heart InstituteUniversity, hospital or other
- Study start
- Sep 2014
- Primary completion
- Sep 2015 (actual)
- Study completion
- Sep 2015 (actual)
- First posted
- 13 Aug 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Pulmonary hypertension or elevation of the pressure in the pulmonary vessels, results from various clinical conditions. It may be idiopathic (of unknown cause) or associated with numerous diseases including cardiovascular and lung disorders. Affected individuals suffer from progressive shortness of breath and, in its most sever forms; pulmonary hypertension carries a worse prognosis than many types of cancer. There is no test currently that can easily and non-invasively detect abnormalities of the pulmonary circulation. Presently there is no cure for pulmonary hypertension and substantial research efforts are dedicated to the development of new drugs that will stop progression or better yet, reverse the disease process. The investigators do not know if any of the drugs currently commercialized for pulmonary hypertension directly improve the status of the pulmonary vessels since no test currently provides this information. Direct earlier detection of lung vessel abnormalities associated with pulmonary hypertension using a sensitive and non-invasive test would allow not only earlier testing of these and of new drugs, but would provide a much better surrogate of disease severity allowing more efficient pre-clinical drug testing. The aim of this phase II study is to evaluate the safety of PulmoBind in participants with pulmonary hypertension and its potential to detect abnormal pulmonary circulation associated within pulmonary hypertension.
Detailed description
Currently there is only one radiopharmaceutical agent approved in Canada (and the world) for clinical imaging of the pulmonary circulation, metastable isotope 99 of technetium. This agent is exclusively used for the diagnosis of physical defects of the circulation due to pulmonary embolus. There is imperative need for new lung tracers that will provide a greater safety profile while enabling functional as well as anatomical imaging of the pulmonary circulation. A novel adrenomedullin derivative has been developed, for molecular imaging of the pulmonary circulation. PulmoBind is labelled with metastable isotope 99 of technetium, the most commonly used imaging isotope in clinical nuclear medicine. PulmoBind is a adrenomedullin derivative specifically designed to bind to the adrenomedullin receptor while avoiding any hemodynamic effects. This novel tracer has the potential to help in the diagnosis and follow-up of various disorders of the pulmonary circulation for which there is currently no alternative. In PulmoBind I three escalating doses were administered and safety was assessed. The product was well tolerated and there were no safety concerns. Imaging revealed predominant lung uptake.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pulmonary Hypertension Patients | Experimental | Drug: PulmoBindPulmoBind is a peptide derived from human adrenomedullin (hAM1-52), labelled with 99mTc (imaging isotope used in clinical medicine). |
| Control Non-Smoking Participants | Active comparator | Drug: PulmoBindPulmoBind is a peptide derived from human adrenomedullin (hAM1-52), labelled with 99mTc (imaging isotope used in clinical medicine). |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- Male of female participants greater than 18 years of age,
- Female participants must be post-menopausal (defined as two year after last menstrual cycle) or surgically sterilized or use 1 form of contraception with a urine negative pregnancy test (commercial brand: first response kit) within 2 hours of study drug injection,
- Baseline measurements must be within limits of normal or judged non-clinically significant by the investigator:
- Male of female participants greater than 18 years of age and upper age 70,
- Female participants must be post-menopausal (defined as two year after last menstrual cycle) or surgically sterilized or use 1 form of contraception with a urine negative pregnancy test (commercial brand: first response kit) within 2 hours of study drug injection,
Key exclusion criteria (27 listed)
- Any known chronic or acute medical condition with or without the need for chronic pharmacologic therapy or any condition that may interfere with normal biodistribution of PulmoBind. This includes but is not restricted to: lung parenchymal or lung vascular diseases such as chronic obstructive pulmonary disease, bronchitis, lung cancer, pleural effusion, emphysema, asthma, pulmonary fibrosis, occupational lung disease,pulmonary hypertension (primary or secondary), systemic hypertension, diabetes, cancer, kidney disease, liver disease, heart failure or previous myocardial infarction, coronary artery disease, peripheral vascular disease or inflammatory disease,
- Participants requiring chronic administration of any substance for a medical condition,
- Active smoking or history of smoking within 6 months,
- Alcoholism or known substance abuse,
- Psychotic,addictive or other disorder limiting the ability to provide informed consent or to comply with study requirements,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PulmoBindPulmoBind is a peptide derived from human adrenomedullin (hAM1-52), labelled with 99mTc (imaging isotope used in clinical medicine). | Drug | Control Non-Smoking Participants, Pulmonary Hypertension Patients |
Primary outcome
To determine the absence of allergic reaction after repeated exposures to PulmoBind in healthy participants
Time frame: Static lung uptake 10 minutes duration post injection
To determine the safety of PulmoBind in participants diagnosed with pulmonary hypertension.
Time frame: Static lung uptake 10 minutes duration post injection
To determine the capacity of PulmoBind lung scan for the detection of abnormal pulmonary circulation associated with pulmonary hypertension.
Time frame: Status lung uptake 10 minutes duration post injection
This is an efficacy outcome
3 secondary outcomes
To determine the intra-subject variability for quantification of PulmoBind lung uptake in control participants
Time frame: Status lung uptake 10 minutes duration post injection
Determine the capacity of PulmoBind lung scan to diagnose pulmonary perfusion defects in participants with chronic thromboembolic pulmonary hypertension.
Time frame: Status lung uptake 10 minutes duration post injection
To correlate lung PulmoBind scan results with parameters of the severity of pulmonary hypertension: 6 minutes walking distance, New York Heart Association functional class, pulmonary artery pressure measured by echo, pulmonary artery pressure measured by
Time frame: Status lung uptake 10 minutes duration post injection
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Sep 2015.
- Derived from this study: PubMed 28236024Harel F, Langleben D, Provencher S, Fournier A, Finnerty V, Nguyen QT, Letourneau M, Levac X, Abikhzer G, Guimond J, Mansour A, Guertin MC, Dupuis J. Molecular imaging of the human pulmonary vascular endothelium in pulmonary hypertension: a phase II safety and proof of principle trial. Eur J Nucl Med Mol Imaging. 2017 Jul;44(7):1136-1144. doi: 10.1007/s00259-017-3655-y. Epub 2017 Feb 24.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jocelyn Dupuis, MD principal investigator
Montreal Heart Institute
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing PulmoBind in people with Pulmonary Hypertension, run by Montreal Heart Institute at 3 sites in Canada.
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 25 inclusion and 27 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 30 Sep 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Canada. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
To determine the absence of allergic reaction after repeated exposures to PulmoBind in healthy participants (time frame: Static lung uptake 10 minutes duration post injection). The study lists 3 primary outcomes in all. 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 NCT02216279, which also lists 1 linked publication.
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 30 Sep 2015.