Ischemic StressPhase 1NCT00250185
The Role of Nitrite in Preconditioning Mediated Tolerance to Ischemic Stress
A Phase 1 study testing Sodium Nitrate and Acetylcholine in people with Ischemic Stress and Transient Non-Lethal Ischemia, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
Trial summary
Many studies have shown that if the human body is stressed by a lack of blood flow for a short period of time, the body develops defenses to make the body more resistant to a future stress from lack of blood flow. This natural defense system is called preconditioning. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Ischemic Stress, Transient Non-Lethal Ischemia
- What is being tested?
- Sodium Nitrate and Acetylcholine
- How many people
- 135 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Nov 2005to 9 Jun 2007
- Phase
- Phase 1
- 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 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Subjects must be 18-45 years of age.
- Subject must be in good health.
- Subjects must provide informed, written consent for participation in this study.
- Female subjects of childbearing age must have a negative pregnancy test.
Who cannot join
- Subjects with a history of cardiac, pulmonary, peripheral vascular, or mitochondrial disease or diabetes mellitus.
- Subjects with a history or evidence of present or past hypertension (blood pressure greater than 140/90 mmHg), hypercholesterolemia (LDL cholesterol greater than 160 mg/dL).
- Subjects with abnormal EKG other than sinus bradycardia.
- Subjects who have a history of smoking within three months.
- Subjects with anemia (defined as hemoglobin less than 9 g/dL).
- BMI greater than 30.
Show all 15Show fewer
- Subjects with a history of reaction to a medication or other substance characterized by dyspnea and cyanosis will not participate in this study.
- Subjects with G6PD deficiency.
- Subjects with a baseline methemoglobin level greater than 1.5%.
- Lactating females who are breastfeeding, will not participate since nitrite crosses into breast milk and could cause methemoglobinemia in the infant.
- No volunteer subject will be allowed to take any prescription medication (oral contraceptive agents are allowed). Vitamin supplements, herbal preparations, nutriceuticals or other 'alternative therapies' must be stopped for two weeks prior to study and aspirin, tylenol and NSAIDs must also be discontinued two weeks prior to study.
- Subjects with a blood pressure of less than 90/60 mmHg or mean arterial pressure (MAP) less than 70 mmHg on the study day will be excluded from the protocol.
- Positive for HIV or hepatitis A or B or positive for syphilis.
- Subjects with a history of placement or insertion of any metal devices including pacemakers, cardiac defibrillators, cochlear implants, aneurysm clips, neural stimulators, insulin pumps or foreign bodies, such as, metal shavings will be excluded from participation in the MRS.
- Subjects with a history of claustrophobia or an inability to lie on their backs will be excluded from the MRS sub-study.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Many studies have shown that if the human body is stressed by a lack of blood flow for a short period of time, the body develops defenses to make the body more resistant to a future stress from lack of blood flow. This natural defense system is called preconditioning. Finding medications that have a preconditioning effect to protect against damage from loss of blood flow would be of great help in the treatment of diseases such as heart attacks and stroke that occur because of blockages of blood flow.
Predicting future heart attacks or strokes is very difficult and makes it difficult to study medications that could have a preconditioning effect. However, it has recently been recognized that we can mimic the preconditioning effect in the human arm, by blocking blood flow using a blood pressure cuff under pressure. Here, blowing up the cuff for 5 minutes and then letting the pressure out for 5 minutes and repeating this process twice more (a way to precondition the arm), has been shown to improve blood vessel function in response to a longer period of blood pressure cuff inflation (20 minutes).
Read more
As nitrite, a naturally occurring blood substance, has biological effects suggesting that it may mimic preconditioning. The main objective of this study is to assess whether nitrite is equivalent to preconditioning in its capacity to protect the forearm blood flow in response to a 20 minute blockage of blood flow by blood pressure cuff inflation of the forearm.
We hypothesize that in human subjects the ischemic preconditioning program works through activation of the pool of nitrite in the blood stream. Moreover, we propose that nitrite treatment will improve (1) blood vessel recovery (2) skeletal muscle blood flow and (3) skeletal muscle mitochondrial function and (4) reduce the activation of inflammation in response to the 20 minute stress of blood pressure cuff inflation.
Read the detailed description
Many studies have shown that if the human body is stressed by a lack of blood flow for a short period of time, the body develops defenses to make the body more resistant to a future stress from lack of blood flow. This natural defense system is called preconditioning. Finding medications that have a preconditioning effect to protect against damage from loss of blood flow would be of great help in the treatment of diseases such as heart attacks and stroke that occur because of blockages of blood flow.
Predicting future heart attacks or strokes is very difficult and makes it difficult to study medications that could have a preconditioning effect. However, it has recently been recognized that we can mimic the preconditioning effect in the human arm, by blocking blood flow using a blood pressure cuff under pressure. Here, blowing up the cuff for 5 minutes and then letting the pressure out for 5 minutes and repeating this process twice more (a way to precondition the arm), has been shown to improve blood vessel function in response to a longer period of blood pressure cuff inflation (20 minutes).
As nitrite, a naturally occurring blood substance, has biological effects suggesting that it may mimic preconditioning. The main objective of this study is to assess whether nitrite is equivalent to preconditioning in its capacity to protect the forearm blood flow in response to a 20 minute blockage of blood flow by blood pressure cuff inflation of the forearm.
We hypothesize that in human subjects the ischemic preconditioning program works through activation of the pool of nitrite in the blood stream. Moreover, we propose that nitrite treatment will improve (1) blood vessel recovery (2) skeletal muscle blood flow and (3) skeletal muscle mitochondrial function and (4) reduce the activation of inflammation in response to the 20 minute stress of blood pressure cuff inflation.
- Conditions
- Ischemic Stress, Transient Non-Lethal Ischemia
- Being tested
- Sodium Nitrate, Acetylcholine
- Keywords
- Ischemia Tolerance, Endothelial Function, Forearm Blood Flow, Muscle Recovery, Inflammation, Healthy Volunteer, HV
- Medical subject headings
- Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sodium NitrateDrug
AcetylcholineDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Nov 2005 (estimated)
- Study start1 Nov 2005
- Primary completion9 Jun 2007
- Study completion9 Jun 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Ischemic StressStudies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)The 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 1
- Primary purpose
- Treatment
- Enrolment
- 135 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00250185
- Sponsor's protocol ID
- 060024
- Other IDs
- 06-H-0024
- Status last verified
- 22 Aug 2008
- First submitted
- 5 Nov 2005
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
Dawn B, Bolli R. Role of nitric oxide in myocardial preconditioning. Ann N Y Acad Sci. 2002 May;962:18-41. doi: 10.1111/j.1749-6632.2002.tb04053.x.
PubMed 12076960Gladwin MT, Shelhamer JH, Schechter AN, Pease-Fye ME, Waclawiw MA, Panza JA, Ognibene FP, Cannon RO 3rd. Role of circulating nitrite and S-nitrosohemoglobin in the regulation of regional blood flow in humans. Proc Natl Acad Sci U S A. 2000 Oct 10;97(21):11482-7. doi: 10.1073/pnas.97.21.11482.
PubMed 11027349Zweier JL, Wang P, Samouilov A, Kuppusamy P. Enzyme-independent formation of nitric oxide in biological tissues. Nat Med. 1995 Aug;1(8):804-9. doi: 10.1038/nm0895-804.
PubMed 7585184
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Nitrite in Preconditioning Mediated Tolerance to Ischemic Stress
- ClinicalTrials.gov ID
- NCT00250185
- Acronym / sponsor ID
- 060024
- Conditions
- Ischemic Stress, Transient Non-Lethal Ischemia
- Keywords
- Ischemia Tolerance, Endothelial Function, Forearm Blood Flow, Muscle Recovery, Inflammation, Healthy Volunteer, HV
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 135 participants
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- 1 Nov 2005
- Primary completion
- 9 Jun 2007 (actual)
- Study completion
- 9 Jun 2007 (actual)
- First posted
- 7 Nov 2005 (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.
Many studies have shown that if the human body is stressed by a lack of blood flow for a short period of time, the body develops defenses to make the body more resistant to a future stress from lack of blood flow. This natural defense system is called preconditioning. Finding medications that have a preconditioning effect to protect against damage from loss of blood flow would be of great help in the treatment of diseases such as heart attacks and stroke that occur because of blockages of blood flow.
Predicting future heart attacks or strokes is very difficult and makes it difficult to study medications that could have a preconditioning effect. However, it has recently been recognized that we can mimic the preconditioning effect in the human arm, by blocking blood flow using a blood pressure cuff under pressure. Here, blowing up the cuff for 5 minutes and then letting the pressure out for 5 minutes and repeating this process twice more (a way to precondition the arm), has been shown to improve blood vessel function in response to a longer period of blood pressure cuff inflation (20 minutes).
As nitrite, a naturally occurring blood substance, has biological effects suggesting that it may mimic preconditioning. The main objective of this study is to assess whether nitrite is equivalent to preconditioning in its capacity to protect the forearm blood flow in response to a 20 minute blockage of blood flow by blood pressure cuff inflation of the forearm.
We hypothesize that in human subjects the ischemic preconditioning program works through activation of the pool of nitrite in the blood stream. Moreover, we propose that nitrite treatment will improve (1) blood vessel recovery (2) skeletal muscle blood flow and (3) skeletal muscle mitochondrial function and (4) reduce the activation of inflammation in response to the 20 minute stress of blood pressure cuff inflation.
Detailed description
Many studies have shown that if the human body is stressed by a lack of blood flow for a short period of time, the body develops defenses to make the body more resistant to a future stress from lack of blood flow. This natural defense system is called preconditioning. Finding medications that have a preconditioning effect to protect against damage from loss of blood flow would be of great help in the treatment of diseases such as heart attacks and stroke that occur because of blockages of blood flow.
Predicting future heart attacks or strokes is very difficult and makes it difficult to study medications that could have a preconditioning effect. However, it has recently been recognized that we can mimic the preconditioning effect in the human arm, by blocking blood flow using a blood pressure cuff under pressure. Here, blowing up the cuff for 5 minutes and then letting the pressure out for 5 minutes and repeating this process twice more (a way to precondition the arm), has been shown to improve blood vessel function in response to a longer period of blood pressure cuff inflation (20 minutes).
As nitrite, a naturally occurring blood substance, has biological effects suggesting that it may mimic preconditioning. The main objective of this study is to assess whether nitrite is equivalent to preconditioning in its capacity to protect the forearm blood flow in response to a 20 minute blockage of blood flow by blood pressure cuff inflation of the forearm.
We hypothesize that in human subjects the ischemic preconditioning program works through activation of the pool of nitrite in the blood stream. Moreover, we propose that nitrite treatment will improve (1) blood vessel recovery (2) skeletal muscle blood flow and (3) skeletal muscle mitochondrial function and (4) reduce the activation of inflammation in response to the 20 minute stress of blood pressure cuff inflation.
Study design
- Primary purpose
- Treatment
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Subjects must be 18-45 years of age.
- Subject must be in good health.
- Subjects must provide informed, written consent for participation in this study.
- Female subjects of childbearing age must have a negative pregnancy test.
Key exclusion criteria (15 listed)
- Subjects with a history of cardiac, pulmonary, peripheral vascular, or mitochondrial disease or diabetes mellitus.
- Subjects with a history or evidence of present or past hypertension (blood pressure greater than 140/90 mmHg), hypercholesterolemia (LDL cholesterol greater than 160 mg/dL).
- Subjects with abnormal EKG other than sinus bradycardia.
- Subjects who have a history of smoking within three months.
- Subjects with anemia (defined as hemoglobin less than 9 g/dL).
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 |
|---|---|---|
| Sodium Nitrate | Drug | – |
| Acetylcholine | Drug | – |
Primary outcome
Not reported in the source record.
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 2 Jul 2017.
- Background: PubMed 12076960Dawn B, Bolli R. Role of nitric oxide in myocardial preconditioning. Ann N Y Acad Sci. 2002 May;962:18-41. doi: 10.1111/j.1749-6632.2002.tb04053.x.
- Background: PubMed 11027349Gladwin MT, Shelhamer JH, Schechter AN, Pease-Fye ME, Waclawiw MA, Panza JA, Ognibene FP, Cannon RO 3rd. Role of circulating nitrite and S-nitrosohemoglobin in the regulation of regional blood flow in humans. Proc Natl Acad Sci U S A. 2000 Oct 10;97(21):11482-7. doi: 10.1073/pnas.97.21.11482.
- Background: PubMed 7585184Zweier JL, Wang P, Samouilov A, Kuppusamy P. Enzyme-independent formation of nitric oxide in biological tissues. Nat Med. 1995 Aug;1(8):804-9. doi: 10.1038/nm0895-804.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Sodium Nitrate and Acetylcholine in people with Ischemic Stress and Transient Non-Lethal Ischemia, run by National Heart, Lung, and Blood Institute (NHLBI) 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 4 inclusion and 15 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 2 Jul 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00250185, which also lists 3 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 2 Jul 2017.