Phase-I Study of Radiolabeled DFH-12 (PulmoBind) for Molecular Imaging of the Pulmonary Circulation

NCT ID: NCT01539889

Last Updated: 2014-10-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-12-31
• Study Completion Date: 2013-01-31

Brief Summary

Pulmonary hypertension (PH) can be the result of various clinical conditions. It may be idiopathic or associated with various cardiovascular and lung disorders. Currently there is no test that can non-invasively detect abnormalities of the pulmonary circulation. There is a growing need for a non-invasive method to detect PH. There currently exists only ne agent approved in Canada for clinical imaging of the pulmonary circulation, 99mTc-labeled macroaggregates. This agent is exclusively used for the diagnosis of physical defects of the circulation due to pulmonary embolus. This agent is larger than small pulmonary vessels, limiting its sensitivity to detect small vascular defects, as well as potential infectious risks since albumin macroaggregates are derived from human albumin. There is need then for new lung tracers that could provide a greater safety profile while enabling functional as well as anatomical imaging of the pulmonary circulation. DFH-12 (PulmoBind) is a peptide derived from human adrenomedullin (hAMI-52). Hence the development of this novel AM derivative, PulmoBind, for molecular imaging of the pulmonary circulation. PulmoBind is labeled with 99mTc, the most commonly used imaging isotope in nuclear medicine.

Conditions

Pulmonary Disease; Pulmonary Hypertension

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

DFH-12 PulmoBind

DFH-12 PulmoBind - 3 doses of; 5mCi for 5 subjects, 10mCifor 5 subjects and 15mCi for 10 subject

Group Type: EXPERIMENTAL

99mTC-PulmoBind

Intervention Type: RADIATION

DFH-12 (PulmoBind) is a peptide derived from human adrenomedullin (hAMI-52). Adrenomedullin (AM) is a 52-amino acid peptide produced by many tissues in the body, including the vascular endothelium. 3 radiolabeled doses of PulmoBind will be used in this study (5mCi, 10mCi and 15mCi) 5 healthy subjects per dose for the 5 mci and the 10 mci groups but 10 subjects will be used for the 15 mci group.

Interventions

99mTC-PulmoBind

DFH-12 (PulmoBind) is a peptide derived from human adrenomedullin (hAMI-52). Adrenomedullin (AM) is a 52-amino acid peptide produced by many tissues in the body, including the vascular endothelium. 3 radiolabeled doses of PulmoBind will be used in this study (5mCi, 10mCi and 15mCi) 5 healthy subjects per dose for the 5 mci and the 10 mci groups but 10 subjects will be used for the 15 mci group.

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

• male or female greater than 18 years of age. Female subjects must be post-menopausal (defined as two years after menstrual cycle)
• within normal range for the following: BP systolic 100-140 mmHg and diastolic 50-90 mmHg;
• HR 60-100 beats per minute;
• oral temperature less than 37.6 degrees Centigrade;
• respiratory rate 12-20 breaths per minute;
• normal lung function tests;
• normal echocardiogram including estimation of pulmonary artery systolic pressure;
• normal chest x-ray; Normal electrocardiogram

Exclusion Criteria

• 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 DFH-12. Includes but not limited 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;
• subjects requiring chronic administration of any substance for a medical condition, active smoking or history of smoking for more than one year in the past 10 years, known self-reported alcoholism (active or abstinent);
• unable to tolerate study procedures ex.(venipuncture, movement restrictions during imaging);
• previous nuclear study since one week (to avoid cross-contamination)

• Minimum Eligible Age: 19 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Montreal Heart Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jocelyn Dupuis, MD

Role: STUDY_DIRECTOR

Montreal Heart

Locations

Montreal Heart Institute

Montreal, Quebec, Canada

Countries

Canada

References

Levac X, Harel F, Finnerty V, Nguyen QT, Letourneau M, Marcil S, Fournier A, Dupuis J. Evaluation of pulmonary perfusion by SPECT imaging using an endothelial cell tracer in supine humans and dogs. EJNMMI Res. 2016 Dec;6(1):43. doi: 10.1186/s13550-016-0198-3. Epub 2016 May 27.

Reference Type: DERIVED

PMID: 27234509 (View on PubMed)

Harel F, Levac X, Nguyen QT, Letourneau M, Marcil S, Finnerty V, Cossette M, Fournier A, Dupuis J. Molecular imaging of the human pulmonary vascular endothelium using an adrenomedullin receptor ligand. Mol Imaging. 2015;14. doi: 10.2310/7290.2015.00003.

Reference Type: DERIVED

PMID: 25812438 (View on PubMed)

Other Identifiers

The PulmoBind Safety Trial

Identifier Type: -

Identifier Source: org_study_id