Impacted Third MolarKYNA-3MNCT07644065
Kynurenic Acid and Serotonin as Perioperative Neuroinflammatory Biomarkers in Sequential Third Molar Surgery
A study testing Ibuprofen and Ibuprofen + Gabapentin in people with Impacted Third Molar and Postoperative Pain, run by Plovdiv Medical University at 1 site in Bulgaria.
Trial summary
A prospective cohort of 40 consecutive patients with bilateral impacted mandibular third molars underwent two sequential surgical extractions separated by a two-week interval. Serum kynurenic acid (KYNA) and serotonin were measured preoperatively and 24 hours after each procedure. Read more about this study
- Who is it for?
- Ages 18 to 38 yearsHealthy volunteers can take part
- Conditions the study is for
- Impacted Third Molar, Postoperative Pain, Neuroinflammation
- What is being tested?
- Ibuprofen and Ibuprofen + Gabapentin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteBulgaria
- Study dates
- 16 Oct 2017to 30 Sep 2020
- Phase
- Interventional
- 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 38 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Bilateral impacted mandibular third molars requiring surgical extraction
- Age 18-38 years
- Written informed consent
- Ability to comply with study procedures
Who cannot join
- Systemic inflammatory disease
- Autoimmune disease
- Neurological disease
- Psychiatric disorders
- Chronic pain conditions
- Use of immunomodulatory medications
Show all 11Show fewer
- Use of psychotropic medications
- Use of analgesic medications
- Pregnancy
- Drug hypersensitivity
- Active pericoronitis at enrollment
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Influence of Serotonin and Kynurenic Acid on Postoperative Pain, Neuroinflammation and Anxiety Following Surgical Removal of Impacted Mandibular Third Molars
A prospective cohort of 40 consecutive patients with bilateral impacted mandibular third molars underwent two sequential surgical extractions separated by a two-week interval. Serum kynurenic acid (KYNA) and serotonin were measured preoperatively and 24 hours after each procedure. The study examined longitudinal dynamics of kynurenine pathway biomarkers, their variation across Pederson surgical difficulty grades, and their relationship with postoperative pain and state anxiety.
Read the detailed description
Participants were randomised to placebo, ibuprofen 400 mg, or ibuprofen 400 mg plus gabapentin 300 mg administered preemptively 1 hour before incision and continued at 8-hourly intervals for 24 hours. Blood samples were collected at four timepoints (T0 Op1, T24 Op1, T0 Op2, T24 Op2) and analysed by ELISA for serum KYNA and serotonin. Postoperative pain was assessed by VAS at 2, 6, 12, 24, 48, and 72 hours. State-trait anxiety was assessed using the STAI Form Y before each operation. Pederson difficulty index was applied independently by two calibrated examiners. The biomarker analysis is reported observationally with pharmacological allocation treated as a covariate. Clinical data and samples were collected at the Department of Oral Surgery, Faculty of Dental Medicine, Medical University of Plovdiv, Bulgaria, during 2017-2018; laboratory biomarker analyses were conducted under Project No. DPDT-12/2019, Medical University of Plovdiv, and completed in 2020.
- Conditions
- Impacted Third Molar, Postoperative Pain, Neuroinflammation, Anxiety
- Being tested
- Placebo, Ibuprofen, Ibuprofen + Gabapentin
- Keywords
- kynurenic acid, serotonin, kynurenine pathway, IDO, third molar surgery, perioperative biomarker, Pederson index, postoperative pain
- Medical subject headings
- Pain, Postoperative, Neuroinflammatory Diseases, Anxiety Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Identical-appearing oral capsules administered preemptively 1 hour before incision and every 8 hours for 24 hours.
IbuprofenDrug
Ibuprofen 400 mg oral capsules administered preemptively 1 hour before incision and every 8 hours for 24 hours.
Ibuprofen + GabapentinDrug
Ibuprofen 400 mg plus Gabapentin 300 mg oral capsules administered preemptively 1 hour before incision and every 8 hours for 24 hours.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Identical-appearing capsules administered 1 hour before incision, repeated every 8 hours for 24 hours. N=10. Receives: Drug: Placebo |
| Ibuprofen | Active comparator | Ibuprofen 400 mg oral capsules administered 1 hour before incision, repeated every 8 hours for 24 hours. N=15 Receives: Drug: Ibuprofen |
| Ibuprofen + Gabapentin | Experimental | Ibuprofen 400 mg plus Gabapentin 300 mg oral capsules administered 1 hour before incision, repeated every 8 hours for 24 hours. N=15 Receives: Drug: Ibuprofen + Gabapentin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Serum kynurenic acid (KYNA) concentration
Change in serum KYNA from preoperative baseline (T0) to 24 hours postoperative (T24) at each of two sequential operations, assessed by ELISA
Measured: Preoperative baseline and 24 hours postoperative at each operation
Serum serotonin concentration
Change in serum serotonin from preoperative baseline (T0) to 24 hours postoperative (T24) at each of two sequential operations, assessed by ELISA
Measured: Preoperative baseline and 24 hours postoperative at each operation
Secondary outcomes (3)
Postoperative pain intensity
Pain assessed using a 100 mm Visual Analogue Scale (VAS; 0 = no pain, 100 = worst imaginable pain)
Measured: 3, 6, 24, 48, and 72 hours postoperatively at each operation
State anxiety
Preoperative state anxiety assessed using the State-Trait Anxiety Inventory (STAI Form Y), State subscale
Measured: Preoperative baseline at each operation
KYNA variation across Pederson surgical difficulty grades
Serum KYNA at 24 hours postoperative compared across Pederson difficulty grades (5-9), assessed by Kruskal-Wallis test
Measured: 24 hours postoperative at Operation 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jun 2026
- Study start16 Oct 2017
- Primary completion17 May 2020
- Study completion30 Sep 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Impacted Third MolarStudies 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 N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Each participant underwent two sequential surgical procedures (bilateral impacted mandibular third molar extractions) separated by a two-week interval, serving as their own control across both operative exposures.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Plovdiv Medical University
- Sponsor type
- University, hospital or other
- Collaborators
- Radka Ivanova Masaldzhieva, Dept. of Health Care Management, Faculty of Public Health, MU-Plovdiv, Mariya Vlado Ivanovska, Dept. of Microbiology and Immunology, Faculty of Medicine, MU-Plovdiv, Ralitsa Dimitrova Raycheva, Dept. of Social Medicine and Public Health, Faculty of Public Health, MU-Plovdiv
- Responsible party
- Principal investigator, Deyan Neychev, Plovdiv Medical University
- Investigators
- Deyan Neychev, MD, PhD, Principal investigator, Medical University of Plovdiv
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07644065
- Sponsor's protocol ID
- DPDT-12/2019
- Other IDs
- Protocol No. P-604/28.02.2020
- Acronym
- KYNA-3M
- Status last verified
- Jun 2026
- First submitted
- 8 Jun 2026
- Last updated
- 7 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data are not planned for public sharing. Anonymized data are available from the corresponding author on reasonable request.
Study at a glance
From the registry record, last updated by the sponsor on 7 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Influence of Serotonin and Kynurenic Acid on Postoperative Pain, Neuroinflammation and Anxiety Following Surgical Removal of Impacted Mandibular Third Molars
- ClinicalTrials.gov ID
- NCT07644065
- Acronym / sponsor ID
- KYNA-3M / DPDT-12/2019
- Conditions
- Impacted Third Molar, Postoperative Pain, Neuroinflammation, Anxiety
- Keywords
- kynurenic acid, serotonin, kynurenine pathway, IDO, third molar surgery, perioperative biomarker, Pederson index, postoperative pain
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Plovdiv Medical UniversityUniversity, hospital or other
- Collaborators
- Radka Ivanova Masaldzhieva, Dept. of Health Care Management, Faculty of Public Health, MU-Plovdiv, Mariya Vlado Ivanovska, Dept. of Microbiology and Immunology, Faculty of Medicine, MU-Plovdiv, Ralitsa Dimitrova Raycheva, Dept. of Social Medicine and Public Health, Faculty of Public Health, MU-Plovdiv
- Study start
- 16 Oct 2017 (actual)
- Primary completion
- 17 May 2020 (actual)
- Study completion
- 30 Sep 2020 (actual)
- First posted
- 12 Jun 2026 (actual)
- 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.
A prospective cohort of 40 consecutive patients with bilateral impacted mandibular third molars underwent two sequential surgical extractions separated by a two-week interval. Serum kynurenic acid (KYNA) and serotonin were measured preoperatively and 24 hours after each procedure. The study examined longitudinal dynamics of kynurenine pathway biomarkers, their variation across Pederson surgical difficulty grades, and their relationship with postoperative pain and state anxiety.
Detailed description
Participants were randomised to placebo, ibuprofen 400 mg, or ibuprofen 400 mg plus gabapentin 300 mg administered preemptively 1 hour before incision and continued at 8-hourly intervals for 24 hours. Blood samples were collected at four timepoints (T0 Op1, T24 Op1, T0 Op2, T24 Op2) and analysed by ELISA for serum KYNA and serotonin. Postoperative pain was assessed by VAS at 2, 6, 12, 24, 48, and 72 hours. State-trait anxiety was assessed using the STAI Form Y before each operation. Pederson difficulty index was applied independently by two calibrated examiners. The biomarker analysis is reported observationally with pharmacological allocation treated as a covariate. Clinical data and samples were collected at the Department of Oral Surgery, Faculty of Dental Medicine, Medical University of Plovdiv, Bulgaria, during 2017-2018; laboratory biomarker analyses were conducted under Project No. DPDT-12/2019, Medical University of Plovdiv, and completed in 2020.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- Each participant underwent two sequential surgical procedures (bilateral impacted mandibular third molar extractions) separated by a two-week interval, serving as their own control across both operative exposures.
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboIdentical-appearing capsules administered 1 hour before incision, repeated every 8 hours for 24 hours. N=10. |
| Ibuprofen | Active comparator | Drug: IbuprofenIbuprofen 400 mg oral capsules administered 1 hour before incision, repeated every 8 hours for 24 hours. N=15 |
| Ibuprofen + Gabapentin | Experimental | Drug: Ibuprofen + GabapentinIbuprofen 400 mg plus Gabapentin 300 mg oral capsules administered 1 hour before incision, repeated every 8 hours for 24 hours. N=15 |
Who may qualify
- Ages
- 18 to 38 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Bilateral impacted mandibular third molars requiring surgical extraction
- Age 18-38 years
- Written informed consent
- Ability to comply with study procedures
Key exclusion criteria (11 listed)
- Systemic inflammatory disease
- Autoimmune disease
- Neurological disease
- Psychiatric disorders
- Chronic pain conditions
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 |
|---|---|---|
| PlaceboIdentical-appearing oral capsules administered preemptively 1 hour before incision and every 8 hours for 24 hours. | Drug | Placebo |
| IbuprofenIbuprofen 400 mg oral capsules administered preemptively 1 hour before incision and every 8 hours for 24 hours. | Drug | Ibuprofen |
| Ibuprofen + GabapentinIbuprofen 400 mg plus Gabapentin 300 mg oral capsules administered preemptively 1 hour before incision and every 8 hours for 24 hours. | Drug | Ibuprofen + Gabapentin |
Primary outcome
Serum kynurenic acid (KYNA) concentration
Time frame: Preoperative baseline and 24 hours postoperative at each operation
Change in serum KYNA from preoperative baseline (T0) to 24 hours postoperative (T24) at each of two sequential operations, assessed by ELISA
Serum serotonin concentration
Time frame: Preoperative baseline and 24 hours postoperative at each operation
Change in serum serotonin from preoperative baseline (T0) to 24 hours postoperative (T24) at each of two sequential operations, assessed by ELISA
3 secondary outcomes
Postoperative pain intensity
Time frame: 3, 6, 24, 48, and 72 hours postoperatively at each operation
State anxiety
Time frame: Preoperative baseline at each operation
KYNA variation across Pederson surgical difficulty grades
Time frame: 24 hours postoperative at Operation 1
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 7 Oct 2026.
- Individual participant dataSharing planned: No. Individual participant data are not planned for public sharing. Anonymized data are available from the corresponding author on reasonable request.
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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.
Deyan Neychev, MD, PhD principal investigator
Medical University of Plovdiv
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Ibuprofen and Ibuprofen + Gabapentin in people with Impacted Third Molar and Postoperative Pain, run by Plovdiv Medical University at 1 site in Bulgaria.
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 11 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 7 Oct 2026. 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 Bulgaria. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
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.
What does the primary outcome measure?
Serum kynurenic acid (KYNA) concentration (time frame: Preoperative baseline and 24 hours postoperative at each operation). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 7 Oct 2026.