PainPhase 2NCT00121563
Evaluation of a TNF-Alpha Modulator for Clinical and Molecular Indicators of Analgesic Effect
A Phase 2 study testing Thalidomide, Ibuprofen or Diazepam in people with Pain, run by National Institute of Nursing Research (NINR) at 1 site in United States.
Trial summary
This study will evaluate the role of thalidomide, a tumor necrosis factor (TNF)-alpha modulator, on severe inflammation and relief of pain following extraction of wisdom teeth. TNFs are substances that affect the pathways of pain. Read more about this study
- Who is it for?
- Any age, men only
- Conditions the study is for
- Pain
- What is being tested?
- Thalidomide, Ibuprofen or Diazepam
- How many people
- 90 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2005to 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
- Men only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- male patients referred for extraction of third molars willing to undergo surgical extraction of all indicated third molars
- a minimum of one partial-bony impacted third molar, with a total difficulty score total of not less than 8
- between the ages of 16 to 35 years (based upon eruption patterns and age-related complications associated with surgical extraction of third molars)
- in good general health- ASA status 1 or 2 (healthy subjects based upon criteria for safe outpatient conscious sedation)
- willing to undergo observation period for six hours postoperatively
Who cannot join
- females
- current mental disorder or substance abuse
- allergy to aspirin, NSAIDs, or sulfonamide
- history of peptic ulcers and GI bleeding
- concurrent use of agents which may potentiate the sedative effect of study drugs, alcohol, opioids, benzodiazapines
- chronic use of medications confounding assessment of the inflammatory response or analgesia, antihistamines, NSAIDs, steroids, antidepressants
Show all 10Show fewer
- presence of chronic debilitating disease (such as diabetes, rheumatoid arthritis, liver disease, etc.)
- presence of symptomatic tooth suggesting infection or inflammation
- excessive surgical difficulty encountered during the surgical procedure, resulting in a difficulty score of 5 for any tooth
- patients with acute narrow angle glaucoma, and open angle glaucoma who are not receiving therapy
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: Evaluation of TNF-Alpha Modulator for Clinical and Molecular Indicators of Analgesic Effect
This study will evaluate the role of thalidomide, a tumor necrosis factor (TNF)-alpha modulator, on severe inflammation and relief of pain following extraction of wisdom teeth. TNFs are substances that affect the pathways of pain. This study involves an experimental group in which patients will be given thalidomide or a placebo (an inactive substance); a negative control group receiving the medication diazepam or a placebo; and a positive control group receiving diazepam or ibuprofen.
Patients who are males ages 16 to 35, who are not allergic to aspirin or other nonsteroidal anti-inflammatory drugs (known as NSAIDs), sulfites, or certain anesthetics, and who in good health may be eligible for this study. Females are not eligible, owing to the risks that thalidomide presents to unborn children. To minimize the risk of fetal malformations, male patients who participate must use a condom during sexual intercourse for 4 weeks following the study and must not donate blood for 4 weeks.
Read more
The medications used in the study will be given 1 hour before surgery. Then after the wisdom teeth are removed, a small piece of tubing will be placed into both sides of the patient's mouth where the teeth were removed. Every 20 minutes, for the next 6 hours, the researchers will collect inflammatory fluid from the tubing, to measure for changes in anti-inflammatory action. If they request pain relievers, patients will receive the medication ketorolac (Toradol), used for short-term treatment of moderately severe acute pain. Side effects of thalidomide include fatigue, dizziness, and rash. The use of ibuprofen and ketorolac may include the risk of gastrointestinal ulcers and bleeding. Diazepam can cause involuntary muscle movements and drowsiness, as well as dizziness lasting for up to 24 hours after it has been used as sedation. Patients will be instructed not to try to walk alone or to try to drive a vehicle during that period. Other risks related to participation in this study include those usually experienced with removal of wisdom teeth-that is, pain and swelling, bruising from insertion of the sedative into a vein (if needed), possible infection at the extraction site, prolonged bleeding, and numbness.
Benefits from participating are having wisdom teeth removed at no cost as well as close monitoring before and after surgery. Results from the study may help people in the future by improving the management of pain following surgery.
Read the detailed description
The proposed investigation is a randomized, double-blind, placebo and positive-controlled clinical study to evaluate the role of the cytokine tumor necrosis factor alpha (TNF-alpha) modulator, thalidomide, in acute inflammation and analgesia. The analgesic effect of thalidomide, a putative TNF-alpha modulator, will be evaluated using a model of tissue injury, the oral surgery model. Briefly, healthy males referred for third molar extraction will undergo the surgical extraction of third molars using standard surgical methods. At the completion of the surgical procedure, a microdialysis probe will be placed under the mucogingival flap previously elevated for the surgical procedure and subjects will be observed for pain over the course of six hours following surgery. Thalidomide or control will be administered one hour prior to surgery. Tissue levels of pro-inflammatory cytokines, and inflammatory mediators will be measured at time intervals postoperatively concomitant with pain measurements. Pain will be assessed postoperatively over the course of six hours. Demonstration of amelioration of pain is the primary outcome measure; changes in levels of tissue mediators will be taken as evidence of an acute anti-inflammatory effect of thalidomide. Based on our previous work with the fusion protein etanercept (TNFR:fc) which specifically binds TNF-alpha and prevents its interaction with cellular receptors, similar changes in the inflammatory cascade and clinical endpoints of inflammation may provide insight into the activity of thalidomide on acute inflammation and its clinical sequela, pain.
- Conditions
- Pain
- Being tested
- Thalidomide, Ibuprofen or Diazepam
- Keywords
- Cytokines, Inflammation, Pain, Injury, Peripheral, Wisdom Teeth, Third Molar Extraction
- Medical subject headings
- Pain, Inflammation, Wounds and Injuries
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Thalidomide, Ibuprofen or DiazepamDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2005 (estimated)
- Study startJul 2005
- 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 PainStudies 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
- NCT00121563
- Sponsor's protocol ID
- 050193
- Other IDs
- 05-NR-0193
- Status last verified
- Feb 2006
- First submitted
- 20 Jul 2005
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
Anthonsen MW, Solhaug A, Johansen B. Functional coupling between secretory and cytosolic phospholipase A2 modulates tumor necrosis factor-alpha- and interleukin-1beta-induced NF-kappa B activation. J Biol Chem. 2001 Aug 10;276(32):30527-36. doi: 10.1074/jbc.M008481200. Epub 2001 Jun 4.
PubMed 11390371Barosi G, Grossi A, Comotti B, Musto P, Gamba G, Marchetti M. Safety and efficacy of thalidomide in patients with myelofibrosis with myeloid metaplasia. Br J Haematol. 2001 Jul;114(1):78-83. doi: 10.1046/j.1365-2141.2001.02918.x.
PubMed 11472348Bastuji-Garin S, Ochonisky S, Bouche P, Gherardi RK, Duguet C, Djerradine Z, Poli F, Revuz J; Thalidomide Neuropathy Study Group. Incidence and risk factors for thalidomide neuropathy: a prospective study of 135 dermatologic patients. J Invest Dermatol. 2002 Nov;119(5):1020-6. doi: 10.1046/j.1523-1747.2002.19502.x.
PubMed 12445187
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
- Evaluation of TNF-Alpha Modulator for Clinical and Molecular Indicators of Analgesic Effect
- ClinicalTrials.gov ID
- NCT00121563
- Acronym / sponsor ID
- 050193
- Conditions
- Pain
- Keywords
- Cytokines, Inflammation, Pain, Injury, Peripheral, Wisdom Teeth, Third Molar Extraction
- 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
- Jul 2005
- Study completion
- Feb 2006
- First posted
- 21 Jul 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.
This study will evaluate the role of thalidomide, a tumor necrosis factor (TNF)-alpha modulator, on severe inflammation and relief of pain following extraction of wisdom teeth. TNFs are substances that affect the pathways of pain. This study involves an experimental group in which patients will be given thalidomide or a placebo (an inactive substance); a negative control group receiving the medication diazepam or a placebo; and a positive control group receiving diazepam or ibuprofen.
Patients who are males ages 16 to 35, who are not allergic to aspirin or other nonsteroidal anti-inflammatory drugs (known as NSAIDs), sulfites, or certain anesthetics, and who in good health may be eligible for this study. Females are not eligible, owing to the risks that thalidomide presents to unborn children. To minimize the risk of fetal malformations, male patients who participate must use a condom during sexual intercourse for 4 weeks following the study and must not donate blood for 4 weeks.
The medications used in the study will be given 1 hour before surgery. Then after the wisdom teeth are removed, a small piece of tubing will be placed into both sides of the patient's mouth where the teeth were removed. Every 20 minutes, for the next 6 hours, the researchers will collect inflammatory fluid from the tubing, to measure for changes in anti-inflammatory action. If they request pain relievers, patients will receive the medication ketorolac (Toradol), used for short-term treatment of moderately severe acute pain. Side effects of thalidomide include fatigue, dizziness, and rash. The use of ibuprofen and ketorolac may include the risk of gastrointestinal ulcers and bleeding. Diazepam can cause involuntary muscle movements and drowsiness, as well as dizziness lasting for up to 24 hours after it has been used as sedation. Patients will be instructed not to try to walk alone or to try to drive a vehicle during that period. Other risks related to participation in this study include those usually experienced with removal of wisdom teeth-that is, pain and swelling, bruising from insertion of the sedative into a vein (if needed), possible infection at the extraction site, prolonged bleeding, and numbness.
Benefits from participating are having wisdom teeth removed at no cost as well as close monitoring before and after surgery. Results from the study may help people in the future by improving the management of pain following surgery.
Detailed description
The proposed investigation is a randomized, double-blind, placebo and positive-controlled clinical study to evaluate the role of the cytokine tumor necrosis factor alpha (TNF-alpha) modulator, thalidomide, in acute inflammation and analgesia. The analgesic effect of thalidomide, a putative TNF-alpha modulator, will be evaluated using a model of tissue injury, the oral surgery model. Briefly, healthy males referred for third molar extraction will undergo the surgical extraction of third molars using standard surgical methods. At the completion of the surgical procedure, a microdialysis probe will be placed under the mucogingival flap previously elevated for the surgical procedure and subjects will be observed for pain over the course of six hours following surgery. Thalidomide or control will be administered one hour prior to surgery. Tissue levels of pro-inflammatory cytokines, and inflammatory mediators will be measured at time intervals postoperatively concomitant with pain measurements. Pain will be assessed postoperatively over the course of six hours. Demonstration of amelioration of pain is the primary outcome measure; changes in levels of tissue mediators will be taken as evidence of an acute anti-inflammatory effect of thalidomide. Based on our previous work with the fusion protein etanercept (TNFR:fc) which specifically binds TNF-alpha and prevents its interaction with cellular receptors, similar changes in the inflammatory cascade and clinical endpoints of inflammation may provide insight into the activity of thalidomide on acute inflammation and its clinical sequela, pain.
Study design
- Primary purpose
- Treatment
Who may qualify
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- male patients referred for extraction of third molars willing to undergo surgical extraction of all indicated third molars
- a minimum of one partial-bony impacted third molar, with a total difficulty score total of not less than 8
- between the ages of 16 to 35 years (based upon eruption patterns and age-related complications associated with surgical extraction of third molars)
- in good general health- ASA status 1 or 2 (healthy subjects based upon criteria for safe outpatient conscious sedation)
- willing to undergo observation period for six hours postoperatively
Key exclusion criteria (10 listed)
- females
- current mental disorder or substance abuse
- allergy to aspirin, NSAIDs, or sulfonamide
- history of peptic ulcers and GI bleeding
- concurrent use of agents which may potentiate the sedative effect of study drugs, alcohol, opioids, benzodiazapines
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 |
|---|---|---|
| Thalidomide, Ibuprofen or Diazepam | 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 4 Mar 2008.
- Background: PubMed 11390371Anthonsen MW, Solhaug A, Johansen B. Functional coupling between secretory and cytosolic phospholipase A2 modulates tumor necrosis factor-alpha- and interleukin-1beta-induced NF-kappa B activation. J Biol Chem. 2001 Aug 10;276(32):30527-36. doi: 10.1074/jbc.M008481200. Epub 2001 Jun 4.
- Background: PubMed 11472348Barosi G, Grossi A, Comotti B, Musto P, Gamba G, Marchetti M. Safety and efficacy of thalidomide in patients with myelofibrosis with myeloid metaplasia. Br J Haematol. 2001 Jul;114(1):78-83. doi: 10.1046/j.1365-2141.2001.02918.x.
- Background: PubMed 12445187Bastuji-Garin S, Ochonisky S, Bouche P, Gherardi RK, Duguet C, Djerradine Z, Poli F, Revuz J; Thalidomide Neuropathy Study Group. Incidence and risk factors for thalidomide neuropathy: a prospective study of 135 dermatologic patients. J Invest Dermatol. 2002 Nov;119(5):1020-6. doi: 10.1046/j.1523-1747.2002.19502.x.
Related trials for Pain
Not yet recruiting
Effect of Stress Ball Use During Femoral Arterial Sheath Removal After Coronary Angiography
Femoral Arterial Sheath Removal, Stress Ball
Recruiting
Empowered Relief® for Cancer Survivors With Chronic Pain
Chronic Pain Due to Cancer, Pain Catastrophizing
RecruitingPhase 4
ESP Blocks for Posterior Spinal Fusion
Postoperative Pain
RecruitingObservational study
Pain Phenotypes in Individuals With Multiple Sclerosis
Multiple Sclerosis, Chronic Pain
Not yet recruiting
Effects of Hip Hinge Exercises on Pain, Range of Motion and Functional Disability in Non-specific Low Back Pain.
Low Back Pain
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 Thalidomide, Ibuprofen or Diazepam in people with Pain, 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 5 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 NCT00121563, 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.