Pain PerceptionPhase 1NCT06847880
The Potential Effect of the Local Administration of Vitamins C and E on Orthodontic Treatment: A Randomized Clinical Trial
A Phase 1 study testing 1: Vitamin C Supplementation and Vitamin E Supplementation in people with Pain Perception and Root Resorption, run by University of Baghdad at 3 sites in Iraq.
Trial summary
Brief Summary of the Study This study investigates the effects of locally administered vitamins C and E on orthodontic tooth movement during the initial stage of treatment. Orthodontic tooth movement relies on bone remodeling, which can be influenced by antioxidants like vitamins C and E. Read more about this study
- Who is it for?
- Ages 12 years and olderHealthy volunteers can take part
- Conditions the study is for
- Pain Perception, Root Resorption, Rate of Orthodontic Tooth Movement
- What is being tested?
- 1: Vitamin C Supplementation and Vitamin E Supplementation
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 56 participants
- Where
- 3 sitesIraq
- Study dates
- 27 Feb 2025to 28 Mar 2026
- 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 12 years and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- Patients aged 12 years and above, who are indicated for fixed appliance orthodontic treatment.
- Patients with moderate to very severe crowding of the mandibular anterior teeth as per the Little's Irregularity Index (LII).
- Treatment with or without two mandibular first premolars extraction. Presence of all the mandibular permanent teeth, except the third molars.
- 5. The overbite and overjet should not impede bracket placement on the mandibular anterior teeth.
Who cannot join
- History of previous orthodontic intervention.
- History of trauma or root resorption in the mandibular anterior teeth.
- Presence of mandibular anterior teeth crowding of less than 4 mm (LII).
- Existence of blocked-out teeth precluding engagement with the aligning archwire.
- History of systemic diseases, especially diabetes and bone diseases.
- Patients with periodontitis and obvious loss of tooth attachment according to Plaque and Bleeding on Probing indices.
Show all 9Show fewer
- Pregnant and lactating mothers.
- Mouth breathing patients and smokers.
- Healthy patients who have not used any medications (such as anti-inflammatory or antimicrobial drugs) or supplements (such as vitamins)
Trial locations and contacts
3 sites in 1 country.
Iraq3 sites
Baghdad Al-Karkh Health Directorate, Baghdad, Iraq
Baghdad, Baghdad Governorate, 10013
Baghdad Al-Rusafa Health Directorate
Baghdad, Baghdad Governorate, 10061
College of Dentistry, University of Baghdad, Baghdad, Iraq
Baghdad, Baghdad Governorate, 10071
About this study
Brief Summary of the Study
This study investigates the effects of locally administered vitamins C and E on orthodontic tooth movement during the initial stage of treatment. Orthodontic tooth movement relies on bone remodeling, which can be influenced by antioxidants like vitamins C and E. Vitamin C promotes collagen formation and osteoblast activity, while vitamin E has anti-inflammatory and antioxidant properties that may impact bone metabolism.
Read more
The study is a randomized clinical trial conducted in multiple clinics, where patients will be divided into three groups:
- Control group - receives a saline injection.
- Vitamin C group - receives a local injection of vitamin C.
- Vitamin E group - receives a local injection of vitamin E.
Injections will be administered every two weeks for vitamin C and every month for vitamin E, for six months, while patients undergo orthodontic treatment with fixed appliances. Researchers will evaluate the rate of tooth movement, root resorption, pain perception, and patient experience. Additionally, biomarkers related to bone remodeling will be measured in gingival crevicular fluid at different time points.
The study aims to determine whether local administration of vitamins C or E enhances orthodontic tooth movement and elevate their effects on the orthodontic potential side effects like root resorption and pain. The findings may provide valuable insights into optimizing orthodontic treatment with the help of antioxidants.
Read the detailed description
This randomized clinical trial aims to investigate the effects of locally administered vitamins C and E on mandibular incisor crowding relief during the initial stage of orthodontic treatment. The study follows a multicenter, prospective, single-blind, parallel-group design with equal randomization (1:1:1) and is conducted at Bab Al-Muadham Dental Health Center and the Postgraduate Orthodontic Clinic, Department of Orthodontics, College of Dentistry, University of Baghdad. Participants were blinded to group allocation, while the principal investigator (A.M.H.) was aware of all group allocations throughout the study period.
Study Rationale Orthodontic tooth movement involves a complex biological process mediated by bone remodeling, which is regulated by mechanical forces and biochemical mediators. Oxidative stress and inflammatory responses play a significant role in the remodeling process. Vitamin C (ascorbic acid) and vitamin E (tocopherol) are known for their antioxidant properties and potential effects on bone metabolism, tissue healing, and inflammation modulation. This study aims to determine whether locally administered vitamins C and E can enhance orthodontic tooth movement, reduce adverse effects such as root resorption, and improve patient experience during treatment.
Study Objectives The primary objective is to compare the effectiveness of vitamin C and vitamin E injections versus a saline control in mandibular incisor crowding relief over 24 weeks.
The secondary objectives include:
Assessing the extent of apical root resorption using periapical radiographs. Evaluating pain perception using a 0-10 numerical rating scale (NRS) during the first seven days after each archwire placement.
Measuring patient perception of treatment experience through a structured questionnaire.
Analyzing levels of biomarkers associated with bone remodeling (RANKL, OPG, RUNX2) in gingival crevicular fluid (GCF) to determine the biological effects of the interventions.
Participant Selection Eligible participants are patients aged 12 years and older with moderate to very severe mandibular anterior crowding (Little's Irregularity Index [LII]). Exclusion criteria include systemic diseases, prior orthodontic treatment, or the use of medications that could influence bone metabolism or inflammatory responses.
Intervention Groups
Participants will be randomly assigned to one of three groups:
Control Group: Receives 0.6 mL of normal saline, divided among the six mandibular anterior teeth and administered every two weeks.
Vitamin C Group: Receives intraepidermal injection of vitamin C (120 mg in 1.2 mL, divided among six mandibular anterior teeth).
Vitamin E Group: Receives intraepidermal injection of vitamin E (15 mg in 0.1 mL, divided among six mandibular anterior teeth).
Injections are repeated biweekly for the vitamin C and control groups and monthly for the vitamin E group, for a total of six months (24 weeks).
A pilot phase included 10 participants. Four participants who received the initial vitamin E regimen of 60 mg in 0.4 mL every two weeks were excluded from the final analysis after the regimen was modified because of poor absorption of the oil-based formulation. The final vitamin E regimen was reduced to 15 mg in 0.1 mL and administered once monthly. The remaining participants in the vitamin C and control groups continued in the trial and were included in the final analysis.
Orthodontic Treatment Protocol
All participants undergo standardized orthodontic treatment using MBT brackets (0.022-inch slot). The leveling and alignment phase follows a sequential archwire progression with CuNiTi archwires in the following sequence:
0.014-inch CuNiTi (weeks 0-8) 0.016-inch CuNiTi (weeks 8-16) 0.018-inch CuNiTi (weeks 16-24)
Data Collection and Outcome Assessments
Data will be collected at multiple time points throughout the study:
- Mandibular Incisor Crowding Relief Direct intraoral scans obtained using the Heron™ intraoral scanner will be used to measure Little's Irregularity Index (LII) at baseline and every four weeks until week 24.
- Root Resorption Standardized periapical radiographs of both mandibular central incisors will be taken at baseline, 8 weeks, and 24 weeks. Root resorption will be assessed using corrected root-length measurements and the Malmgren scoring index.
- Pain Perception Participants will record the maximum mandibular tooth pain experienced once daily in the evening using a 0-10 NRS for seven days after each archwire placement.
- Patient Perception A 22-item bilingual questionnaire assessing pain, discomfort, swelling, numbness, functional difficulties, effects on daily activities, and overall perception of the intervention visit will be administered at 8 weeks.
- Biomarker Analysis Gingival crevicular fluid (GCF) samples will be collected at baseline, 1 week, and 4 weeks. Levels of RANKL, OPG, and RUNX2 will be analyzed to assess changes in bone remodeling activity.
Statistical Analysis
Data will be analyzed using SPSS version 26. Statistical methods will include:
Descriptive statistics (mean, standard deviation, frequency). Intraclass correlation coefficients and weighted kappa statistics for measurement reliability.
One-way analysis of variance, mixed-design repeated-measures analysis of variance, Kruskal-Wallis test, Wilcoxon signed-rank test, Pearson's chi-square test, and Friedman test.
A significance level of 0.05 will be used for hypothesis testing, with Bonferroni adjustment where applicable.
Study Oversight and Ethical Considerations The study is self-funded and complies with ethical guidelines for human research. Ethical approval was obtained from the Research Ethics Committee of the College of Dentistry, University of Baghdad, on 21 January 2025 (reference number 1014; project number 1014425). Written informed consent was obtained from adult participants. For participants younger than 18 years, written parental or guardian consent and participant assent were obtained before enrolment.
Potential Impact This trial may provide valuable insights into the role of antioxidant therapy in orthodontic treatment. If vitamins C and E positively influence tooth movement and root integrity, their use could enhance treatment efficiency while minimizing complications. Findings may also contribute to a better understanding of bone remodeling mechanisms in response to mechanical forces.
- Being tested
- 1: Vitamin C Supplementation, Vitamin E Supplementation, Saline Solution (Control)
- Keywords
- Orthodontic tooth movement, Root resorption, RANKL, Tooth alignment, Vitamin C, Vitamin E, Pain perception, Osteoprotegerin, RUNX2
- Medical subject headings
- Root Resorption
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
1: Vitamin C SupplementationDrug
- Vitamin C (Ascorbic Acid): This intervention involves the administration of vitamin C, which is known for its antioxidant properties. The concentration will be 120 mg in 1.2 ml, and the produced volume will be divided by six lower anterior teeth; each tooth will receive 0.2 ml (20 mg) of the vitamin C. It is hypothesized to accelerate orthodontic tooth movement by reducing oxidative stress and promoting collagen synthesis.
Vitamin E SupplementationDrug
- Vitamin E (Tocopherol Acetate): This intervention uses vitamin E, another antioxidant, thought to reduce inflammation and support tissue repair, potentially improving the effectiveness of orthodontic treatment by enhancing tissue recovery and reducing side effects. The total dose was 15 mg in 0.1 mL, divided among the six mandibular anterior teeth; each tooth received 2.5 mg in approximately 0.02 mL. Vitamin E was administered once monthly for 24 weeks.
Saline Solution (Control)Other
Saline Solution (Control): The control group will receive a saline solution, which is a placebo, allowing for the comparison of the effects of vitamin C and vitamin E on orthodontic tooth movement without the influence of additional nutrients.
| Study group | Role | What they receive |
|---|---|---|
| Arm 1: Vitamin C Treatment | Experimental | This arm involves participants receiving Vitamin C to assess its effect on orthodontic tooth movement and crowding relief. The treatment aims to evaluate how Vitamin C influences the rate of tooth movement, as measured by Little's Irregularity Index (LII) over 24 weeks (the supposed end date of leveling and alignment stage). Receives: Drug: 1: Vitamin C Supplementation |
| Vitamin E Treatment | Experimental | Participants in this arm will receive Vitamin E to evaluate its effect on orthodontic tooth movement. The aim is to compare the efficacy of Vitamin E to Vitamin C and the saline control in terms of crowding relief and tooth alignment, measured using LII over a 24-week period (the supposed end date of leveling and alignment stage). Receives: Drug: Vitamin E Supplementation |
| Arm 3: Saline Control | Placebo comparator | This arm serves as the control group, where participants receive saline injections. The primary aim is to assess how saline compares with Vitamin C and Vitamin E treatments in terms of the rate of orthodontic tooth movement and crowding relief as measured by LII. Receives: Other: Saline Solution (Control) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in the amount of crowding relief of the mandibular incisors before treatment and at 4, 8, 12, 16, 20, and 24 weeks after the start of treatment among the two vitamins and control groups
The amount of crowding relief will be measured using Little's Irregularity Index (LII) on 3D digital models of the mandibular anterior teeth. Pre-treatment (T0) and post-treatment models at 4, 8, 12, 16, 20, and 24 weeks will be compared.
- Measurement method: Alginate impressions will be taken at each time point and converted into 3D digital models using a high-precision scanner.
- Definition: LII quantifies anterior misalignment by summing the displacement between mesial and distal contact points of six mandibular incisors.
- Units: Millimeters (mm), rounded to 0.01 mm.
- Expected outcome: Greater LII reduction indicates a higher rate of tooth movement.
- Comparison: The control (saline) group will be compared with the vitamin C and vitamin E groups to assess their effects on tooth movement.
Measured: The amount of crowding relief will be measured using Little's Irregularity Index (LII) on 3D digital models of the mandibular anterior teeth. Measurements will be taken at baseline (T0) and at 4, 8, 12, 16, 20, and 24 weeks to assess changes over time.
Secondary outcomes (4)
Pain Perception After Archwire Placement: A Visual Analog Scale Assessment
Pain perception will be measured using a Visual Analog Scale (VAS), a commonly used tool in clinical settings to quantify subjective pain experiences. The VAS consists of a 10 cm line where participants mark their pain level. One end of the line represents "no pain" (score of 0), and the other end represents "worst pain imaginable" (score of 10). Participants will be asked to record their pain levels twice daily for the first 7 days following each archwire placement during the treatment phase.
Measured: From the placement of each archwire to 7 days post-placement.
Amount of orthodontically-induced inflammatory root resorption (OIIRR) in the apical region of mandibular anterior teeth
Measurement of the root resorption in the apical region of the mandibular anterior teeth, assessed through radiographs and calculated by comparing the root length and crown length.
Measured: Pre-treatment (T0), 8 weeks (T1), and 24 weeks (T2) after the start of treatment.
Patient perception using a newly developed questionnaire for adjunctive orthodontic therapy
Patients will complete a questionnaire to assess their perception of the treatment's comfort, side effects, and any additional effects due to vitamin administration during orthodontic therapy.
Measured: 8 weeks after the start of treatment.
Levels of biomarkers (RANKL, OPG, and RUNX2) in gingival crevicular fluid (GCF):
Measurement of the biomarkers in the GCF, which are involved in bone turnover and remodeling. These markers will help assess the biological effects of the vitamins on periodontal tissues during the initial stage of orthodontic treatment.
Measured: Pre-treatment (T0), 1 week (T1), and 4 weeks (T2) after the start of treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Feb 2025
- Study start27 Feb 2025
- Primary completion28 Feb 2026
- Study completion28 Mar 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Pain PerceptionStudies of the same condition, open and under way.
- More trials run by University of BaghdadThe 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
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This multicenter, prospective, randomized clinical trial follows a parallel-group design (1:1:1) with single blinding. Patients and operators are blinded, but the investigator (A.M.H.) is not. Participants are randomly assigned to one of three groups: (1) Control (saline injection), (2) Vitamin C (ascorbic acid injection), or (3) Vitamin E (alpha-tocopherol injection). Randomization uses a computer-based generator with stratification, and allocation is concealed in sealed containers. Orthodontic tooth movement, root resorption, pain perception, and biomarker levels will be measured at baseline and every four weeks up to 24 weeks. Vitamin injections are administered biweekly for six months (the supposed end date of leveling and alignment stage).
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 56 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Baghdad
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ayat M. Hussein, University of Baghdad
- Investigators
- Professor Dr. Yassir Abdulkadhim Yassir, Ph.D. (Orthodontics) (UK), Study director, University of Baghdad
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06847880
- Sponsor's protocol ID
- 1014425
- Status last verified
- Jul 2026
- First submitted
- 1 Feb 2025
- Last updated
- 3 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Bolat E, Esenlik E, Oncu M, Ozgocmen M, Avunduk MC, Yuksel O. Evaluation of the effects of vitamins C and E on experimental orthodontic tooth movement. J Dent Res Dent Clin Dent Prospects. 2020 Spring;14(2):131-137. doi: 10.34172/joddd.2020.0027. Epub 2020 Jun 17.
PubMed 32908655Yussif, N. (2019). Oral Mesotherapy: might be considered as an adjunctive technique for the different surgical procedures?. In Periodontal disease-diagnostic and adjunctive non-surgical considerations. IntechOpen.
Yussif, N.M.A., Dehis, H.M., Rahman, A.R.A., Aziz, M.A.W.M.A. and Yassin, M.M. (2018). Efficacy and safety of locally injectable vitamin C on accelerating the orthodontic movement of maxillary canine impaction (oral mesotherapy technique): prospective study. Clinical Cases in Mineral & Bone Metabolism, 15(2).
Mohsin MK, Qadir Omer Z. The effect of vitamin E incorporated into injectable platelet-rich fibrin on orthodontic tooth movement in rabbits. Cell Mol Biol (Noisy-le-grand). 2024 Jun 5;70(6):147-154. doi: 10.14715/cmb/2024.70.6.23.
PubMed 38836668Kappus H, Diplock AT. Tolerance and safety of vitamin E: a toxicological position report. Free Radic Biol Med. 1992;13(1):55-74. doi: 10.1016/0891-5849(92)90166-e.
PubMed 1628854Esenlik E, Naziroglu M, Acikalin C, Ovey IS. Vitamin E supplementation modulates gingival crevicular fluid lipid peroxidation and antioxidant levels in patients with orthodontic tooth movement. Cell Biochem Funct. 2012 Jul;30(5):376-81. doi: 10.1002/cbf.1833. Epub 2011 Nov 24.
PubMed 22113708Carr AC, Lykkesfeldt J. Discrepancies in global vitamin C recommendations: a review of RDA criteria and underlying health perspectives. Crit Rev Food Sci Nutr. 2021;61(5):742-755. doi: 10.1080/10408398.2020.1744513. Epub 2020 Mar 30.
PubMed 32223303Mucklow, J.C. (2000). Martindale: the complete drug reference. British journal of clinical pharmacology, 49(6), p.613.
Hathcock JN, Azzi A, Blumberg J, Bray T, Dickinson A, Frei B, Jialal I, Johnston CS, Kelly FJ, Kraemer K, Packer L, Parthasarathy S, Sies H, Traber MG. Vitamins E and C are safe across a broad range of intakes. Am J Clin Nutr. 2005 Apr;81(4):736-45. doi: 10.1093/ajcn/81.4.736.
PubMed 15817846
Study at a glance
From the registry record, last updated by the sponsor on 3 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Potential Effect of the Local Administration of Vitamins C and E on Orthodontic Treatment: A Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT06847880
- Acronym / sponsor ID
- 1014425
- Keywords
- Orthodontic tooth movement, Root resorption, RANKL, Tooth alignment, Vitamin C, Vitamin E, Pain perception, Osteoprotegerin
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants (actual)
- Lead sponsor
- University of BaghdadUniversity, hospital or other
- Study start
- 27 Feb 2025 (actual)
- Primary completion
- 28 Feb 2026 (actual)
- Study completion
- 28 Mar 2026 (actual)
- First posted
- 26 Feb 2025 (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.
Brief Summary of the Study
This study investigates the effects of locally administered vitamins C and E on orthodontic tooth movement during the initial stage of treatment. Orthodontic tooth movement relies on bone remodeling, which can be influenced by antioxidants like vitamins C and E. Vitamin C promotes collagen formation and osteoblast activity, while vitamin E has anti-inflammatory and antioxidant properties that may impact bone metabolism.
The study is a randomized clinical trial conducted in multiple clinics, where patients will be divided into three groups:
- Control group - receives a saline injection.
- Vitamin C group - receives a local injection of vitamin C.
- Vitamin E group - receives a local injection of vitamin E.
Injections will be administered every two weeks for vitamin C and every month for vitamin E, for six months, while patients undergo orthodontic treatment with fixed appliances. Researchers will evaluate the rate of tooth movement, root resorption, pain perception, and patient experience. Additionally, biomarkers related to bone remodeling will be measured in gingival crevicular fluid at different time points.
The study aims to determine whether local administration of vitamins C or E enhances orthodontic tooth movement and elevate their effects on the orthodontic potential side effects like root resorption and pain. The findings may provide valuable insights into optimizing orthodontic treatment with the help of antioxidants.
Detailed description
This randomized clinical trial aims to investigate the effects of locally administered vitamins C and E on mandibular incisor crowding relief during the initial stage of orthodontic treatment. The study follows a multicenter, prospective, single-blind, parallel-group design with equal randomization (1:1:1) and is conducted at Bab Al-Muadham Dental Health Center and the Postgraduate Orthodontic Clinic, Department of Orthodontics, College of Dentistry, University of Baghdad. Participants were blinded to group allocation, while the principal investigator (A.M.H.) was aware of all group allocations throughout the study period.
Study Rationale Orthodontic tooth movement involves a complex biological process mediated by bone remodeling, which is regulated by mechanical forces and biochemical mediators. Oxidative stress and inflammatory responses play a significant role in the remodeling process. Vitamin C (ascorbic acid) and vitamin E (tocopherol) are known for their antioxidant properties and potential effects on bone metabolism, tissue healing, and inflammation modulation. This study aims to determine whether locally administered vitamins C and E can enhance orthodontic tooth movement, reduce adverse effects such as root resorption, and improve patient experience during treatment.
Study Objectives The primary objective is to compare the effectiveness of vitamin C and vitamin E injections versus a saline control in mandibular incisor crowding relief over 24 weeks.
The secondary objectives include:
Assessing the extent of apical root resorption using periapical radiographs. Evaluating pain perception using a 0-10 numerical rating scale (NRS) during the first seven days after each archwire placement.
Measuring patient perception of treatment experience through a structured questionnaire.
Analyzing levels of biomarkers associated with bone remodeling (RANKL, OPG, RUNX2) in gingival crevicular fluid (GCF) to determine the biological effects of the interventions.
Participant Selection Eligible participants are patients aged 12 years and older with moderate to very severe mandibular anterior crowding (Little's Irregularity Index [LII]). Exclusion criteria include systemic diseases, prior orthodontic treatment, or the use of medications that could influence bone metabolism or inflammatory responses.
Intervention Groups
Participants will be randomly assigned to one of three groups:
Control Group: Receives 0.6 mL of normal saline, divided among the six mandibular anterior teeth and administered every two weeks.
Vitamin C Group: Receives intraepidermal injection of vitamin C (120 mg in 1.2 mL, divided among six mandibular anterior teeth).
Vitamin E Group: Receives intraepidermal injection of vitamin E (15 mg in 0.1 mL, divided among six mandibular anterior teeth).
Injections are repeated biweekly for the vitamin C and control groups and monthly for the vitamin E group, for a total of six months (24 weeks).
A pilot phase included 10 participants. Four participants who received the initial vitamin E regimen of 60 mg in 0.4 mL every two weeks were excluded from the final analysis after the regimen was modified because of poor absorption of the oil-based formulation. The final vitamin E regimen was reduced to 15 mg in 0.1 mL and administered once monthly. The remaining participants in the vitamin C and control groups continued in the trial and were included in the final analysis.
Orthodontic Treatment Protocol
All participants undergo standardized orthodontic treatment using MBT brackets (0.022-inch slot). The leveling and alignment phase follows a sequential archwire progression with CuNiTi archwires in the following sequence:
0.014-inch CuNiTi (weeks 0-8) 0.016-inch CuNiTi (weeks 8-16) 0.018-inch CuNiTi (weeks 16-24)
Data Collection and Outcome Assessments
Data will be collected at multiple time points throughout the study:
- Mandibular Incisor Crowding Relief Direct intraoral scans obtained using the Heron™ intraoral scanner will be used to measure Little's Irregularity Index (LII) at baseline and every four weeks until week 24.
- Root Resorption Standardized periapical radiographs of both mandibular central incisors will be taken at baseline, 8 weeks, and 24 weeks. Root resorption will be assessed using corrected root-length measurements and the Malmgren scoring index.
- Pain Perception Participants will record the maximum mandibular tooth pain experienced once daily in the evening using a 0-10 NRS for seven days after each archwire placement.
- Patient Perception A 22-item bilingual questionnaire assessing pain, discomfort, swelling, numbness, functional difficulties, effects on daily activities, and overall perception of the intervention visit will be administered at 8 weeks.
- Biomarker Analysis Gingival crevicular fluid (GCF) samples will be collected at baseline, 1 week, and 4 weeks. Levels of RANKL, OPG, and RUNX2 will be analyzed to assess changes in bone remodeling activity.
Statistical Analysis
Data will be analyzed using SPSS version 26. Statistical methods will include:
Descriptive statistics (mean, standard deviation, frequency). Intraclass correlation coefficients and weighted kappa statistics for measurement reliability.
One-way analysis of variance, mixed-design repeated-measures analysis of variance, Kruskal-Wallis test, Wilcoxon signed-rank test, Pearson's chi-square test, and Friedman test.
A significance level of 0.05 will be used for hypothesis testing, with Bonferroni adjustment where applicable.
Study Oversight and Ethical Considerations The study is self-funded and complies with ethical guidelines for human research. Ethical approval was obtained from the Research Ethics Committee of the College of Dentistry, University of Baghdad, on 21 January 2025 (reference number 1014; project number 1014425). Written informed consent was obtained from adult participants. For participants younger than 18 years, written parental or guardian consent and participant assent were obtained before enrolment.
Potential Impact This trial may provide valuable insights into the role of antioxidant therapy in orthodontic treatment. If vitamins C and E positively influence tooth movement and root integrity, their use could enhance treatment efficiency while minimizing complications. Findings may also contribute to a better understanding of bone remodeling mechanisms in response to mechanical forces.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 3
- Model description
- This multicenter, prospective, randomized clinical trial follows a parallel-group design (1:1:1) with single blinding. Patients and operators are blinded, but the investigator (A.M.H.) is not. Participants are randomly assigned to one of three groups: (1) Control (saline injection), (2) Vitamin C (ascorbic acid injection), or (3) Vitamin E (alpha-tocopherol injection). Randomization uses a computer-based generator with stratification, and allocation is concealed in sealed containers. Orthodontic tooth movement, root resorption, pain perception, and biomarker levels will be measured at baseline and every four weeks up to 24 weeks. Vitamin injections are administered biweekly for six months (the supposed end date of leveling and alignment stage).
| Arm | Type | Receives |
|---|---|---|
| Arm 1: Vitamin C Treatment | Experimental | Drug: 1: Vitamin C SupplementationThis arm involves participants receiving Vitamin C to assess its effect on orthodontic tooth movement and crowding relief. The treatment aims to evaluate how Vitamin C influences the rate of tooth movement, as measured by Little's Irregularity Index (LII) over 24 weeks (the supposed end date of leveling and alignment stage). |
| Vitamin E Treatment | Experimental | Drug: Vitamin E SupplementationParticipants in this arm will receive Vitamin E to evaluate its effect on orthodontic tooth movement. The aim is to compare the efficacy of Vitamin E to Vitamin C and the saline control in terms of crowding relief and tooth alignment, measured using LII over a 24-week period (the supposed end date of leveling and alignment stage). |
| Arm 3: Saline Control | Placebo comparator | Other: Saline Solution (Control)This arm serves as the control group, where participants receive saline injections. The primary aim is to assess how saline compares with Vitamin C and Vitamin E treatments in terms of the rate of orthodontic tooth movement and crowding relief as measured by LII. |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- Patients aged 12 years and above, who are indicated for fixed appliance orthodontic treatment.
- Patients with moderate to very severe crowding of the mandibular anterior teeth as per the Little's Irregularity Index (LII).
- Treatment with or without two mandibular first premolars extraction. Presence of all the mandibular permanent teeth, except the third molars.
- 5. The overbite and overjet should not impede bracket placement on the mandibular anterior teeth.
Key exclusion criteria (9 listed)
- History of previous orthodontic intervention.
- History of trauma or root resorption in the mandibular anterior teeth.
- Presence of mandibular anterior teeth crowding of less than 4 mm (LII).
- Existence of blocked-out teeth precluding engagement with the aligning archwire.
- History of systemic diseases, especially diabetes and bone diseases.
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 |
|---|---|---|
| 1: Vitamin C Supplementation• Vitamin C (Ascorbic Acid): This intervention involves the administration of vitamin C, which is known for its antioxidant properties. The concentration will be 120 mg in 1.2 ml, and the produced volume will be divided by six lower anterior teeth; each tooth will receive 0.2 ml (20 mg) of the vitamin C. It is hypothesized to accelerate orthodontic tooth movement by reducing oxidative stress and promoting collagen synthesis. | Drug | Arm 1: Vitamin C Treatment |
| Vitamin E Supplementation• Vitamin E (Tocopherol Acetate): This intervention uses vitamin E, another antioxidant, thought to reduce inflammation and support tissue repair, potentially improving the effectiveness of orthodontic treatment by enhancing tissue recovery and reducing side effects. The total dose was 15 mg in 0.1 mL, divided among the six mandibular anterior teeth; each tooth received 2.5 mg in approximately 0.02 mL. Vitamin E was administered once monthly for 24 weeks. | Drug | Vitamin E Treatment |
| Saline Solution (Control)Saline Solution (Control): The control group will receive a saline solution, which is a placebo, allowing for the comparison of the effects of vitamin C and vitamin E on orthodontic tooth movement without the influence of additional nutrients. | Other | Arm 3: Saline Control |
Primary outcome
Difference in the amount of crowding relief of the mandibular incisors before treatment and at 4, 8, 12, 16, 20, and 24 weeks after the start of treatment among the two vitamins and control groups
Time frame: The amount of crowding relief will be measured using Little's Irregularity Index (LII) on 3D digital models of the mandibular anterior teeth. Measurements will be taken at baseline (T0) and at 4, 8, 12, 16, 20, and 24 weeks to assess changes over time.
The amount of crowding relief will be measured using Little's Irregularity Index (LII) on 3D digital models of the mandibular anterior teeth. Pre-treatment (T0) and post-treatment models at 4, 8, 12, 16, 20, and 24 weeks will be compared. * Measurement method: Alginate impressions will be taken at each time point and converted into 3D digital models using a high-precision scanner. * Definition: LII quantifies anterior misalignment by summing the displacement between mesial and distal contact points of six mandibular incisors. * Units: Millimeters (mm), rounded to 0.01 mm. * Expected outcome: Greater LII reduction indicates a higher rate of tooth movement. * Comparison: The control (saline) group will be compared with the vitamin C and vitamin E groups to assess their effects on tooth movement.
4 secondary outcomes
Pain Perception After Archwire Placement: A Visual Analog Scale Assessment
Time frame: From the placement of each archwire to 7 days post-placement.
Amount of orthodontically-induced inflammatory root resorption (OIIRR) in the apical region of mandibular anterior teeth
Time frame: Pre-treatment (T0), 8 weeks (T1), and 24 weeks (T2) after the start of treatment.
Patient perception using a newly developed questionnaire for adjunctive orthodontic therapy
Time frame: 8 weeks after the start of treatment.
Levels of biomarkers (RANKL, OPG, and RUNX2) in gingival crevicular fluid (GCF):
Time frame: Pre-treatment (T0), 1 week (T1), and 4 weeks (T2) after the start of treatment.
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 3 Sep 2026.
- Results publication: PubMed 32908655Bolat E, Esenlik E, Oncu M, Ozgocmen M, Avunduk MC, Yuksel O. Evaluation of the effects of vitamins C and E on experimental orthodontic tooth movement. J Dent Res Dent Clin Dent Prospects. 2020 Spring;14(2):131-137. doi: 10.34172/joddd.2020.0027. Epub 2020 Jun 17.
- Results publicationYussif, N. (2019). Oral Mesotherapy: might be considered as an adjunctive technique for the different surgical procedures?. In Periodontal disease-diagnostic and adjunctive non-surgical considerations. IntechOpen.
- Results publicationYussif, N.M.A., Dehis, H.M., Rahman, A.R.A., Aziz, M.A.W.M.A. and Yassin, M.M. (2018). Efficacy and safety of locally injectable vitamin C on accelerating the orthodontic movement of maxillary canine impaction (oral mesotherapy technique): prospective study. Clinical Cases in Mineral & Bone Metabolism, 15(2).
- Results publication: PubMed 38836668Mohsin MK, Qadir Omer Z. The effect of vitamin E incorporated into injectable platelet-rich fibrin on orthodontic tooth movement in rabbits. Cell Mol Biol (Noisy-le-grand). 2024 Jun 5;70(6):147-154. doi: 10.14715/cmb/2024.70.6.23.
- Results publication: PubMed 1628854Kappus H, Diplock AT. Tolerance and safety of vitamin E: a toxicological position report. Free Radic Biol Med. 1992;13(1):55-74. doi: 10.1016/0891-5849(92)90166-e.
- Results publication: PubMed 22113708Esenlik E, Naziroglu M, Acikalin C, Ovey IS. Vitamin E supplementation modulates gingival crevicular fluid lipid peroxidation and antioxidant levels in patients with orthodontic tooth movement. Cell Biochem Funct. 2012 Jul;30(5):376-81. doi: 10.1002/cbf.1833. Epub 2011 Nov 24.
- Results publication: PubMed 32223303Carr AC, Lykkesfeldt J. Discrepancies in global vitamin C recommendations: a review of RDA criteria and underlying health perspectives. Crit Rev Food Sci Nutr. 2021;61(5):742-755. doi: 10.1080/10408398.2020.1744513. Epub 2020 Mar 30.
- Results publicationMucklow, J.C. (2000). Martindale: the complete drug reference. British journal of clinical pharmacology, 49(6), p.613.
- Results publication: PubMed 15817846Hathcock JN, Azzi A, Blumberg J, Bray T, Dickinson A, Frei B, Jialal I, Johnston CS, Kelly FJ, Kraemer K, Packer L, Parthasarathy S, Sies H, Traber MG. Vitamins E and C are safe across a broad range of intakes. Am J Clin Nutr. 2005 Apr;81(4):736-45. doi: 10.1093/ajcn/81.4.736.
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- 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.
Professor Dr. Yassir Abdulkadhim Yassir, Ph.D. (Orthodontics) (UK) study director
University of Baghdad
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing 1: Vitamin C Supplementation and Vitamin E Supplementation in people with Pain Perception and Root Resorption, run by University of Baghdad at 3 sites in Iraq.
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 9 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 3 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Iraq. 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.
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.
What does the primary outcome measure?
Difference in the amount of crowding relief of the mandibular incisors before treatment and at 4, 8, 12, 16, 20, and 24 weeks after the start of treatment among the two vitamins and control groups (time frame: The amount of crowding relief will be measured using Little's Irregularity Index (LII) on 3D digital models of the mandibular anterior teeth. Measurements will be taken at baseline (T0) and at 4, 8, 12, 16, 20, and 24 weeks to assess changes over time.). 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 NCT06847880, which also lists 9 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 3 Sep 2026.