The Potential Effect of the Local Administration of Vitamins C and E on Orthodontic Treatment: A Randomized Clinical Trial

September 2, 2026 updated by: Ayat M. Hussein, University of Baghdad

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:

  1. Control group - receives a saline injection.
  2. Vitamin C group - receives a local injection of vitamin C.
  3. 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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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:

  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
56

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: Ayat Mohammed Hussein, M.Sc. (Orthodontics)
  • Phone Number: +9647729435382
  • Email: Drayaat420@gmail.com

Study Locations

  • Iraq
    • Baghdad Governorate
      • Baghdad, Baghdad Governorate, Iraq, 10013
        • Baghdad Al-Karkh Health Directorate, Baghdad, Iraq
      • Baghdad, Baghdad Governorate, Iraq, 10061
        • Baghdad Al-Rusafa Health Directorate
      • Baghdad, Baghdad Governorate, Iraq, 10071
        • College of Dentistry, University of Baghdad, Baghdad, Iraq

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  1. Patients aged 12 years and above, who are indicated for fixed appliance orthodontic treatment.
  2. Patients with moderate to very severe crowding of the mandibular anterior teeth as per the Little's Irregularity Index (LII).
  3. 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.

Exclusion Criteria:

  1. History of previous orthodontic intervention.
  2. History of trauma or root resorption in the mandibular anterior teeth.
  3. Presence of mandibular anterior teeth crowding of less than 4 mm (LII).
  4. Existence of blocked-out teeth precluding engagement with the aligning archwire.
  5. History of systemic diseases, especially diabetes and bone diseases.
  6. Patients with periodontitis and obvious loss of tooth attachment according to Plaque and Bleeding on Probing indices.
  7. Pregnant and lactating mothers.
  8. Mouth breathing patients and smokers.
  9. Healthy patients who have not used any medications (such as anti-inflammatory or antimicrobial drugs) or supplements (such as vitamins)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Arm 1: Vitamin C Treatment
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).
Drug: 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.
Experimental: Vitamin E Treatment
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).
Drug: 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.
Placebo Comparator: Arm 3: Saline 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.
Other: 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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Pain Perception After Archwire Placement: A Visual Analog Scale Assessment
Time Frame: From the placement of each archwire to 7 days post-placement.
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.
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.
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.
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.
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.
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.
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.
Pre-treatment (T0), 1 week (T1), and 4 weeks (T2) after the start of treatment.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Baghdad

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Professor Dr. Yassir Abdulkadhim Yassir, Ph.D. (Orthodontics) (UK), University of Baghdad

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 27, 2025

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 28, 2026

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 28, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 1, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 21, 2025

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 26, 2025

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 3, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 2, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 1014425

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings