Tooth, ImpactedPhase 2NCT00083356
Bradykinin Receptors and Pain
A Phase 2 study testing Wisdom tooth extraction in people with Tooth, Impacted, run by National Institute of Nursing Research (NINR) at 1 site in United States.
Trial summary
This study will examine whether bradykinin receptors are produced at the site of wisdom tooth extraction and if they contribute to the amount of inflammation and pain that follows surgery. Bradykinin is a molecule produced by enzymes at the site of an injury and then binds to receptors to cause pain. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Tooth, Impacted
- What is being tested?
- Wisdom tooth extraction
- Type of treatment
- Surgery or procedure
- How many people
- 90 participants
- Where
- 1 siteUnited States
- Study dates
- May 2004to Feb 2006
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Male or female volunteers referred for third molar extraction willing to undergo 2 or 3 visits: 1 screening visit; 1 surgical appointment; and a possible follow-up research-related appointment
- Between the ages of 16 to 35 years (based upon eruption patterns and age-related complications associated with surgical extraction of third molars
- In general good health- American Society of Anesthesiologists (ASA) status I or II (healthy subjects based upon criteria for safe administration of out-patient conscious sedation)
- Willing to undergo observation period for three hours postoperatively
- Ability to complete a 100 mm visual analog scale and a category scale every 20 minutes for the first 3 postoperative hours
- Willing to have a microdialysis probe placed beneath the surgical flap during the first 3 hours post-surgery
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- Willing to have a preoperative biopsy on the day of surgery, and a postoperative biopsy either at 3, 7 or 24 hours following surgery
- Willing to return, if needed, 24 hours post-operation for the postoperative biopsy
- Must have two lower partial (rating is equal to 3) or fully impacted (rating is equal to 4) wisdom teeth (mandibular third molars)
- As assessed at the screening visit, the sum of the mandibular third molar surgical difficulty ratings must be between 6 to 8 in order to evaluate subjects experiencing similar pain levels
Who cannot join
- Patients who are allergic to aspirin, NSAIDs, sulfites, or amide anesthetics
- Patients who have had asthma, or hives
- Patients who are pregnant or nursing
- Patients with history of peptic ulcers and/or GI bleeding
- Chronic use of medications confounding the assessment of the inflammatory response or analgesia, for example, NSAIDs, COX-2 inhibitors, antihistamines, steroids, antidepressants
- Patients who have clinical signs suggestive of infection, inflammation, or pre-existing pain at either extraction site
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- Patients with severe kidney disease
- Patients who are taking any of the following drugs: ACE inhibitor; potassium sparing diuretics; aspirin on a near daily basis; coumadin or other blood thinners
- Patients who are taking drugs known to inhibit P450 2C9 and drugs metabolized by P450 2D6
- Unusual surgical difficulty (determined from panoramic radiograph or during the actual surgery)
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institute of Nursing Research (NINR)
Bethesda, Maryland, 20892
About this study
Official title: Bradykinin-1 Receptor and Kinin Induction in a Clinical Model of Tissue Injury
This study will examine whether bradykinin receptors are produced at the site of wisdom tooth extraction and if they contribute to the amount of inflammation and pain that follows surgery. Bradykinin is a molecule produced by enzymes at the site of an injury and then binds to receptors to cause pain. The study will also evaluate the role of genetic factors in the production of bradykinin and their receptors and the pain associated with minor surgical procedures.
Patients between 16 and 35 years of age who are referred to the NIH dental clinic for removal of two wisdom teeth may be eligible for this study. Candidates must be in good health and must not be allergic to aspirin, non-steroidal anti-inflammatory drugs, sulfites, or amide anesthetics. They will be screened with a medical history and oral examination, including x-rays to confirm the need for wisdom tooth extraction.
Read more
On the morning of surgery following an overnight fast, participants have a blood sample drawn to extract DNA for gene studies. Just before surgery, they are given an intravenous (IV) sedative to induce drowsiness and a local anesthetic to numb the mouth. They are also given IV either Ketorolac, a non-steroidal anti-inflammatory drug, or placebo, a look-alike medication with no active ingredient. After the extractions, a small piece of plastic tubing is placed in both extraction sites, and every 20 minutes for the next 3 hours inflammatory fluid is collected from the tubing for measuring chemicals believed to cause pain and swelling. Patients rate their pain by answering pain-related questions every 20 minutes. Patients who have pain that is not relieved by the study medication (Ketorolac or placebo) are given, upon request, 50 mg of the pain reliever tramadol (Ultram). Patients remain in the clinic for at least 3 hours and no more than 7 hours after surgery in order for monitoring the effects of the study drugs as the local anesthetic wears off.
Patients undergo two biopsies during the study - one before and one after the extraction - to measure any changes in chemicals produced in response to the surgery. The second biopsy is done either 3, 7, or 24 hours after the extraction. Patients in the 3- and 7-hour groups are given a small dose of local anesthetic in the gum for the second biopsy and remain in the clinic until the biopsy is done; those in the 24-hour group are given forms to record pain ratings at home and return to the clinic the following morning for a 2-hour follow-up visit. All patients are given standard pain medication (flurbiprofen) to take at home.
Read the detailed description
Bradykinin B1 receptors and their natural agonists are known to be rapidly induced in local tissues by a variety of inflammatory stimuli. Preclinical evidence, demonstrating that interruption of B1 receptor function causes analgesia under a variety of conditions, has been well established using selective antagonists and genetically modified mice. Accordingly, efforts are underway in several laboratories to develop novel B1 receptor antagonists as potential novel analgesic agents. The proposed studies will examine the kinetics of local induction of B1 receptors and kinin formation in a common situation of acute inflammatory pain in humans - tooth extraction. In addition, an examination of expression of additional genes of interest under these conditions using microarray analysis will be conducted.
- Conditions
- Tooth, Impacted
- Being tested
- Wisdom tooth extraction
- Keywords
- Pain, Kinins, Inflammation, Gene Expression, Oral Surgey, Bradykinin B1 Receptors, Acute Peripheral Inflammation, Inflammatory Gene Expression, Wisdom Teeth, Third Molar Extraction
- Medical subject headings
- Tooth, Impacted, Pain, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Wisdom tooth extractionProcedure or surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 May 2004 (estimated)
- Study startMay 2004
- Study completionFeb 2006
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 Tooth, ImpactedStudies 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
- Treatment
- Enrolment
- 90 participants
Sponsor and investigators
- Lead sponsor
- National Institute of Nursing Research (NINR)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00083356
- Sponsor's protocol ID
- 040182
- Other IDs
- 04-NR-0182
- Status last verified
- Feb 2006
- First submitted
- 21 May 2004
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
Walker K, Perkins M, Dray A. Kinins and kinin receptors in the nervous system. Neurochem Int. 1995 Jan;26(1):1-16; discussion 17-26. doi: 10.1016/0197-0186(94)00114-a.
PubMed 7787759Ahluwalia A, Perretti M. B1 receptors as a new inflammatory target. Could this B the 1? Trends Pharmacol Sci. 1999 Mar;20(3):100-4. doi: 10.1016/s0165-6147(99)01321-8.
PubMed 10203864Bock MG, Longmore J. Bradykinin antagonists: new opportunities. Curr Opin Chem Biol. 2000 Aug;4(4):401-6. doi: 10.1016/s1367-5931(00)00107-1.
PubMed 10959767
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Bradykinin-1 Receptor and Kinin Induction in a Clinical Model of Tissue Injury
- ClinicalTrials.gov ID
- NCT00083356
- Acronym / sponsor ID
- 040182
- Conditions
- Tooth, Impacted
- Keywords
- Pain, Kinins, Inflammation, Gene Expression, Oral Surgey, Bradykinin B1 Receptors, Acute Peripheral Inflammation, Inflammatory Gene Expression
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 90 participants
- Lead sponsor
- National Institute of Nursing Research (NINR)US National Institutes of Health
- Study start
- May 2004
- Study completion
- Feb 2006
- First posted
- 21 May 2004 (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.
This study will examine whether bradykinin receptors are produced at the site of wisdom tooth extraction and if they contribute to the amount of inflammation and pain that follows surgery. Bradykinin is a molecule produced by enzymes at the site of an injury and then binds to receptors to cause pain. The study will also evaluate the role of genetic factors in the production of bradykinin and their receptors and the pain associated with minor surgical procedures.
Patients between 16 and 35 years of age who are referred to the NIH dental clinic for removal of two wisdom teeth may be eligible for this study. Candidates must be in good health and must not be allergic to aspirin, non-steroidal anti-inflammatory drugs, sulfites, or amide anesthetics. They will be screened with a medical history and oral examination, including x-rays to confirm the need for wisdom tooth extraction.
On the morning of surgery following an overnight fast, participants have a blood sample drawn to extract DNA for gene studies. Just before surgery, they are given an intravenous (IV) sedative to induce drowsiness and a local anesthetic to numb the mouth. They are also given IV either Ketorolac, a non-steroidal anti-inflammatory drug, or placebo, a look-alike medication with no active ingredient. After the extractions, a small piece of plastic tubing is placed in both extraction sites, and every 20 minutes for the next 3 hours inflammatory fluid is collected from the tubing for measuring chemicals believed to cause pain and swelling. Patients rate their pain by answering pain-related questions every 20 minutes. Patients who have pain that is not relieved by the study medication (Ketorolac or placebo) are given, upon request, 50 mg of the pain reliever tramadol (Ultram). Patients remain in the clinic for at least 3 hours and no more than 7 hours after surgery in order for monitoring the effects of the study drugs as the local anesthetic wears off.
Patients undergo two biopsies during the study - one before and one after the extraction - to measure any changes in chemicals produced in response to the surgery. The second biopsy is done either 3, 7, or 24 hours after the extraction. Patients in the 3- and 7-hour groups are given a small dose of local anesthetic in the gum for the second biopsy and remain in the clinic until the biopsy is done; those in the 24-hour group are given forms to record pain ratings at home and return to the clinic the following morning for a 2-hour follow-up visit. All patients are given standard pain medication (flurbiprofen) to take at home.
Detailed description
Bradykinin B1 receptors and their natural agonists are known to be rapidly induced in local tissues by a variety of inflammatory stimuli. Preclinical evidence, demonstrating that interruption of B1 receptor function causes analgesia under a variety of conditions, has been well established using selective antagonists and genetically modified mice. Accordingly, efforts are underway in several laboratories to develop novel B1 receptor antagonists as potential novel analgesic agents. The proposed studies will examine the kinetics of local induction of B1 receptors and kinin formation in a common situation of acute inflammatory pain in humans - tooth extraction. In addition, an examination of expression of additional genes of interest under these conditions using microarray analysis will be conducted.
Study design
- Primary purpose
- Treatment
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (10 listed)
- Male or female volunteers referred for third molar extraction willing to undergo 2 or 3 visits: 1 screening visit; 1 surgical appointment; and a possible follow-up research-related appointment
- Between the ages of 16 to 35 years (based upon eruption patterns and age-related complications associated with surgical extraction of third molars
- In general good health- American Society of Anesthesiologists (ASA) status I or II (healthy subjects based upon criteria for safe administration of out-patient conscious sedation)
- Willing to undergo observation period for three hours postoperatively
- Ability to complete a 100 mm visual analog scale and a category scale every 20 minutes for the first 3 postoperative hours
Key exclusion criteria (10 listed)
- Patients who are allergic to aspirin, NSAIDs, sulfites, or amide anesthetics
- Patients who have had asthma, or hives
- Patients who are pregnant or nursing
- Patients with history of peptic ulcers and/or GI bleeding
- Chronic use of medications confounding the assessment of the inflammatory response or analgesia, for example, NSAIDs, COX-2 inhibitors, antihistamines, steroids, antidepressants
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 |
|---|---|---|
| Wisdom tooth extraction | Procedure or surgery | – |
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 4 Mar 2008.
- Background: PubMed 7787759Walker K, Perkins M, Dray A. Kinins and kinin receptors in the nervous system. Neurochem Int. 1995 Jan;26(1):1-16; discussion 17-26. doi: 10.1016/0197-0186(94)00114-a.
- Background: PubMed 10203864Ahluwalia A, Perretti M. B1 receptors as a new inflammatory target. Could this B the 1? Trends Pharmacol Sci. 1999 Mar;20(3):100-4. doi: 10.1016/s0165-6147(99)01321-8.
- Background: PubMed 10959767Bock MG, Longmore J. Bradykinin antagonists: new opportunities. Curr Opin Chem Biol. 2000 Aug;4(4):401-6. doi: 10.1016/s1367-5931(00)00107-1.
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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 2 study testing Wisdom tooth extraction in people with Tooth, Impacted, run by National Institute of Nursing Research (NINR) 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 10 inclusion and 10 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 4 Mar 2008. 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?
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 NCT00083356, 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 4 Mar 2008.