Blood TransfusionPhase 2NCT01529502
Pilot Study About the Harmful Effects of Blood Storage on Overweight People and the Role of iNO in This Setting
A Phase 2 study testing Red blood Cells auto-transfusion and Inhaled Nitric Oxide (iNO) administration in people with Blood Transfusion and Endothelial Physiopathology, run by Massachusetts General Hospital at 1 site in United States.
Trial summary
The purpose of this study is to determine whether storage time affects how human body responds to autologous blood transfusion. An autologous blood transfusion is when a person donates blood and then receives that same blood back in the transfusion. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Blood Transfusion, Endothelial Physiopathology, Nitric Oxide
- What is being tested?
- Red blood Cells auto-transfusion and Inhaled Nitric Oxide (iNO) administration
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2012to Dec 2013
- 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 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Have a photo ID
- Age>18 years old (required to provide informed consent)
- Age <60 years old
- Mild impairment of endothelial function, assessed by post ischemic vasodilation (L_RHI,<0.7) (38)
- Body mass index (BMI) >27 kg/m^2 and <40 kg/m^2
- Fasting during the days of transfusion.
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- Avoiding intake of high nitrate food (i.e. green leafy vegetables: lettuce, spinach) on the day prior to the study
- Feel well on the day of blood donation
- KG within normal limits
- Normotensive (systolic blood pressure <140 mmHg and diastolic <90 mmHg)
- Normal physical exam and blood test results as indicated by:
- WBC 4.5-11.0 n x103/μL
- HGB 12.0-17.5 gm/dl
- PLT 150-400 n x103/μL
- Plasma Sodium 135-145 mmol/L
- Plasma Potassium 3.4-4.8 mmol/L
- Plasma Chloride 98-108 mmol/L
- Plasma Carbon Dioxide 23.0-31.9 mmol/L
- Plasma Urea Nitrogen 8-25 mg/dl
- Plasma Creatinine 0.60-1.50 mg/dl
- Plasma Glucose 70-110 mg/dl
- Transaminase-SGPT 10-55 U/L
- Transaminase-SGOT 10-40 U/L
- Total Bilirubin < 2 mg/dl
- Fasting plasma glucose < 110 mg/dl
- Methemoglobin < 3%
Who cannot join
- Psychiatric disturbances such as anxiety, depression, schizophrenia requiring pharmacological treatment or hospitalization in the last year
- Systemic disease with or without any functional limitation
- Pregnancy determined by urine pregnancy test, detecting presence of human chorionic gonadotropin (hCG), or less than six weeks postpartum
- Active smoking. Volunteers may be enrolled if they quit smoking for more than 1 year.
- Excess alcohol use: more than ½ L/day of wine consumption or equivalent
- Any current use of a medication other than: over-the-counter oral medications, herbal remedies, nutritional supplements, and oral contraceptives.
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- Antibiotic use within 48 hours of blood donation
- Use of NSAIDS, corticosteroids, aspirin during the past 7 days
- Dental work within 24 hours prior to the donation
- Received or donated blood in the last 4 months
- Have had any forms of cancer with the exceptions of basal cell skin cancer or treatment for in situ uterine cervical cancer
- Currently enrolled in another research study
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital
Boston, Massachusetts, 02114
About this study
Official title: Effects of Stored Red Blood Cell Transfusion in Overweight Subjects With Endothelial Dysfunction: Influence of Inhaled Nitric Oxide (iNO)
The purpose of this study is to determine whether storage time affects how human body responds to autologous blood transfusion. An autologous blood transfusion is when a person donates blood and then receives that same blood back in the transfusion. We also want to find out if in this situation inhaled nitric oxide can help to prevent the potential reduction of vasodilation capacity. Vasodilation capacity is the ability of the blood vessel to widen when needed.
Read the detailed description
The objective of this study is to assess effects of the storage of PRBC on pulmonary vasoconstriction measured as increase in pulmonary artery pressure and endothelial function measured as a change in reactive hyperemia index in overweight people with existing endothelial dysfunction at baseline.
The present study consists of three different parts, which will be scheduled in a randomized order on the same subject (crossover study).
During one phase of the study, 14 healthy human volunteers will donate a unit of Packed Red Blood Cells (PRBC), which will be leukoreduced and stored in Additive Solutions-1 (AS-1), and then transfused back to the subjects after 3 days of storage at 4º C in the MGH Blood Bank (Fresh Blood arm). The second part of the study consists in the collection of another unit of PRBC from the same volunteers which will be transfused back to them after 40 days of storage (Old Blood arm). Finally in the third part, like in the second one, one unit of PRBC will be withdraw and stored for 40 days, but 80 ppm (parts per million by volume) Nitric Oxide in air will be administered together with the transfusion. There will be a 2 weeks interval after each PRBC transfusion.
We hypothesize that old red blood cells stored under conventional conditions may trigger a complex, pro-inflammatory, pro-thrombotic and vasoconstriction response. We will compare the response to PRBC stored for 3 days with the response to PRBC stored for 40 days in the same healthy volunteers. We also want to test the hypothesis that inhaled nitric oxide may reverse these adverse effects.
We will monitor/measure the following parameters:
- Pulmonary vasoconstriction by trans-thoracic echocardiography
- Endothelium-mediated changes in vascular (arterial) tone, measured as reactive hyperemia index.
- Being tested
- Red blood Cells auto-transfusion, Inhaled Nitric Oxide (iNO) administration
- Keywords
- Blood Transfusion, Autologous, Blood Preservation/adverse effects, Blood Transfusion/adverse effects, Endothelium, Vascular/physiopathology, Hemoglobins, Nitric Oxide, Pulmonary Hypertension
- Medical subject headings
- Hypertension, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Red blood Cells auto-transfusionProcedure or surgery
Withdrawal from 14 overweight volunteers of one unit of red blood cells and auto-transfusion after 3 days storage time. The same 14 subjects will be included in every arm of the study.
Red blood Cells auto-transfusionProcedure or surgery
Withdrawal from the same 14 overweight volunteers of one unit of red blood cells and auto-transfusion after 40 days storage time.
Inhaled Nitric Oxide (iNO) administrationDrug
Subjects will breath iNO (80ppm) for 10 minutes before, during and for one hour after the autologous old-blood transfusion.
| Study group | Role | What they receive |
|---|---|---|
| Fresh blood | Experimental | Not described Receives: Procedure: Red blood Cells auto-transfusion |
| Old blood | Experimental | Not described Receives: Procedure: Red blood Cells auto-transfusion |
| Old blood + inhaled Nitric Oxide | Experimental | Not described Receives: Procedure: Red blood Cells auto-transfusion; Drug: Inhaled Nitric Oxide (iNO) administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
Systolic Pulmonary Artery Pressure
Pulmonary vasoconstriction was measured by estimation of Systolic Pulmonary Artery Pressure in millimeter of mercury (mmHg) by trans-thoracic echocardiography
Measured: Post-transfusion
Secondary outcomes (1)
Endothelial Function: Reactive Hyperemia Index
Reactive Hyperemia Index (RHI) measures Endothelial function and is assessed by digital pulse amplitude tonometry and it is a sensitive indicator of endothelial function. RHI is a calculated as a ratio between tested versus contralateral finger dilatation, thus there is no unit measure.
Measured: Post-transfusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Feb 2012 (estimated)
- Study startMar 2012
- Primary completionDec 2013
- Study completionDec 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Blood TransfusionStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- 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
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Warren M. Zapol, Massachusetts General Hospital
- Investigators
- Warren Zapol, MD, Principal investigator, Masachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01529502
- Sponsor's protocol ID
- Blood Study Overweight
- Status last verified
- Apr 2017
- First submitted
- 6 Feb 2012
- Last updated
- 22 May 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Hendrickson JE, Hillyer CD. Noninfectious serious hazards of transfusion. Anesth Analg. 2009 Mar;108(3):759-69. doi: 10.1213/ane.0b013e3181930a6e.
PubMed 19224780Koch CG, Li L, Sessler DI, Figueroa P, Hoeltge GA, Mihaljevic T, Blackstone EH. Duration of red-cell storage and complications after cardiac surgery. N Engl J Med. 2008 Mar 20;358(12):1229-39. doi: 10.1056/NEJMoa070403.
PubMed 18354101Bennett-Guerrero E, Veldman TH, Doctor A, Telen MJ, Ortel TL, Reid TS, Mulherin MA, Zhu H, Buck RD, Califf RM, McMahon TJ. Evolution of adverse changes in stored RBCs. Proc Natl Acad Sci U S A. 2007 Oct 23;104(43):17063-8. doi: 10.1073/pnas.0708160104. Epub 2007 Oct 11.
PubMed 17940021Cardillo C, Kilcoyne CM, Cannon RO 3rd, Panza JA. Interactions between nitric oxide and endothelin in the regulation of vascular tone of human resistance vessels in vivo. Hypertension. 2000 Jun;35(6):1237-41. doi: 10.1161/01.hyp.35.6.1237.
PubMed 10856270Panza JA, Casino PR, Kilcoyne CM, Quyyumi AA. Role of endothelium-derived nitric oxide in the abnormal endothelium-dependent vascular relaxation of patients with essential hypertension. Circulation. 1993 May;87(5):1468-74. doi: 10.1161/01.cir.87.5.1468.
PubMed 8491001Hod EA, Brittenham GM, Billote GB, Francis RO, Ginzburg YZ, Hendrickson JE, Jhang J, Schwartz J, Sharma S, Sheth S, Sireci AN, Stephens HL, Stotler BA, Wojczyk BS, Zimring JC, Spitalnik SL. Transfusion of human volunteers with older, stored red blood cells produces extravascular hemolysis and circulating non-transferrin-bound iron. Blood. 2011 Dec 15;118(25):6675-82. doi: 10.1182/blood-2011-08-371849. Epub 2011 Oct 20.
PubMed 22021369Berra L, Pinciroli R, Stowell CP, Wang L, Yu B, Fernandez BO, Feelisch M, Mietto C, Hod EA, Chipman D, Scherrer-Crosbie M, Bloch KD, Zapol WM. Autologous transfusion of stored red blood cells increases pulmonary artery pressure. Am J Respir Crit Care Med. 2014 Oct 1;190(7):800-7. doi: 10.1164/rccm.201405-0850OC.
PubMed 25162920
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Stored Red Blood Cell Transfusion in Overweight Subjects With Endothelial Dysfunction: Influence of Inhaled Nitric Oxide (iNO)
- ClinicalTrials.gov ID
- NCT01529502
- Acronym / sponsor ID
- Blood Study Overweight
- Keywords
- Blood Transfusion, Autologous, Blood Preservation/adverse effects, Blood Transfusion/adverse effects, Endothelium, Vascular/physiopathology, Hemoglobins, Nitric Oxide, Pulmonary Hypertension
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Study start
- Mar 2012
- Primary completion
- Dec 2013 (actual)
- Study completion
- Dec 2013 (actual)
- First posted
- 8 Feb 2012 (estimated)
- Results
- Posted 29 Mar 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine whether storage time affects how human body responds to autologous blood transfusion. An autologous blood transfusion is when a person donates blood and then receives that same blood back in the transfusion. We also want to find out if in this situation inhaled nitric oxide can help to prevent the potential reduction of vasodilation capacity. Vasodilation capacity is the ability of the blood vessel to widen when needed.
Detailed description
The objective of this study is to assess effects of the storage of PRBC on pulmonary vasoconstriction measured as increase in pulmonary artery pressure and endothelial function measured as a change in reactive hyperemia index in overweight people with existing endothelial dysfunction at baseline.
The present study consists of three different parts, which will be scheduled in a randomized order on the same subject (crossover study).
During one phase of the study, 14 healthy human volunteers will donate a unit of Packed Red Blood Cells (PRBC), which will be leukoreduced and stored in Additive Solutions-1 (AS-1), and then transfused back to the subjects after 3 days of storage at 4º C in the MGH Blood Bank (Fresh Blood arm). The second part of the study consists in the collection of another unit of PRBC from the same volunteers which will be transfused back to them after 40 days of storage (Old Blood arm). Finally in the third part, like in the second one, one unit of PRBC will be withdraw and stored for 40 days, but 80 ppm (parts per million by volume) Nitric Oxide in air will be administered together with the transfusion. There will be a 2 weeks interval after each PRBC transfusion.
We hypothesize that old red blood cells stored under conventional conditions may trigger a complex, pro-inflammatory, pro-thrombotic and vasoconstriction response. We will compare the response to PRBC stored for 3 days with the response to PRBC stored for 40 days in the same healthy volunteers. We also want to test the hypothesis that inhaled nitric oxide may reverse these adverse effects.
We will monitor/measure the following parameters:
- Pulmonary vasoconstriction by trans-thoracic echocardiography
- Endothelium-mediated changes in vascular (arterial) tone, measured as reactive hyperemia index.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Fresh blood | Experimental | Procedure: Red blood Cells auto-transfusion |
| Old blood | Experimental | Procedure: Red blood Cells auto-transfusion |
| Old blood + inhaled Nitric Oxide | Experimental | Procedure: Red blood Cells auto-transfusion, Drug: Inhaled Nitric Oxide (iNO) administration |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (26 listed)
- Have a photo ID
- Age>18 years old (required to provide informed consent)
- Age <60 years old
- Mild impairment of endothelial function, assessed by post ischemic vasodilation (L_RHI,<0.7) (38)
- Body mass index (BMI) >27 kg/m^2 and <40 kg/m^2
Key exclusion criteria (12 listed)
- Psychiatric disturbances such as anxiety, depression, schizophrenia requiring pharmacological treatment or hospitalization in the last year
- Systemic disease with or without any functional limitation
- Pregnancy determined by urine pregnancy test, detecting presence of human chorionic gonadotropin (hCG), or less than six weeks postpartum
- Active smoking. Volunteers may be enrolled if they quit smoking for more than 1 year.
- Excess alcohol use: more than ½ L/day of wine consumption or equivalent
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 |
|---|---|---|
| Red blood Cells auto-transfusionWithdrawal from 14 overweight volunteers of one unit of red blood cells and auto-transfusion after 3 days storage time. The same 14 subjects will be included in every arm of the study. | Procedure or surgery | Fresh blood |
| Red blood Cells auto-transfusionWithdrawal from the same 14 overweight volunteers of one unit of red blood cells and auto-transfusion after 40 days storage time. | Procedure or surgery | Old blood, Old blood + inhaled Nitric Oxide |
| Inhaled Nitric Oxide (iNO) administrationSubjects will breath iNO (80ppm) for 10 minutes before, during and for one hour after the autologous old-blood transfusion. | Drug | Old blood + inhaled Nitric Oxide |
Primary outcome
Systolic Pulmonary Artery Pressure
Time frame: Post-transfusion
Pulmonary vasoconstriction was measured by estimation of Systolic Pulmonary Artery Pressure in millimeter of mercury (mmHg) by trans-thoracic echocardiography
1 secondary outcome
Endothelial Function: Reactive Hyperemia Index
Time frame: Post-transfusion
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 May 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 19224780Hendrickson JE, Hillyer CD. Noninfectious serious hazards of transfusion. Anesth Analg. 2009 Mar;108(3):759-69. doi: 10.1213/ane.0b013e3181930a6e.
- Background: PubMed 18354101Koch CG, Li L, Sessler DI, Figueroa P, Hoeltge GA, Mihaljevic T, Blackstone EH. Duration of red-cell storage and complications after cardiac surgery. N Engl J Med. 2008 Mar 20;358(12):1229-39. doi: 10.1056/NEJMoa070403.
- Background: PubMed 17940021Bennett-Guerrero E, Veldman TH, Doctor A, Telen MJ, Ortel TL, Reid TS, Mulherin MA, Zhu H, Buck RD, Califf RM, McMahon TJ. Evolution of adverse changes in stored RBCs. Proc Natl Acad Sci U S A. 2007 Oct 23;104(43):17063-8. doi: 10.1073/pnas.0708160104. Epub 2007 Oct 11.
- Background: PubMed 10856270Cardillo C, Kilcoyne CM, Cannon RO 3rd, Panza JA. Interactions between nitric oxide and endothelin in the regulation of vascular tone of human resistance vessels in vivo. Hypertension. 2000 Jun;35(6):1237-41. doi: 10.1161/01.hyp.35.6.1237.
- Background: PubMed 8491001Panza JA, Casino PR, Kilcoyne CM, Quyyumi AA. Role of endothelium-derived nitric oxide in the abnormal endothelium-dependent vascular relaxation of patients with essential hypertension. Circulation. 1993 May;87(5):1468-74. doi: 10.1161/01.cir.87.5.1468.
- Background: PubMed 22021369Hod EA, Brittenham GM, Billote GB, Francis RO, Ginzburg YZ, Hendrickson JE, Jhang J, Schwartz J, Sharma S, Sheth S, Sireci AN, Stephens HL, Stotler BA, Wojczyk BS, Zimring JC, Spitalnik SL. Transfusion of human volunteers with older, stored red blood cells produces extravascular hemolysis and circulating non-transferrin-bound iron. Blood. 2011 Dec 15;118(25):6675-82. doi: 10.1182/blood-2011-08-371849. Epub 2011 Oct 20.
- Derived from this study: PubMed 25162920Berra L, Pinciroli R, Stowell CP, Wang L, Yu B, Fernandez BO, Feelisch M, Mietto C, Hod EA, Chipman D, Scherrer-Crosbie M, Bloch KD, Zapol WM. Autologous transfusion of stored red blood cells increases pulmonary artery pressure. Am J Respir Crit Care Med. 2014 Oct 1;190(7):800-7. doi: 10.1164/rccm.201405-0850OC.
- Individual participant dataSharing planned: No
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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.
Warren Zapol, MD principal investigator
Masachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Red blood Cells auto-transfusion and Inhaled Nitric Oxide (iNO) administration in people with Blood Transfusion and Endothelial Physiopathology, run by Massachusetts General Hospital 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 26 inclusion and 12 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 22 May 2017. 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 29 Mar 2017). 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?
Systolic Pulmonary Artery Pressure (time frame: Post-transfusion). 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 NCT01529502, which also lists 7 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 22 May 2017.