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

NCT06847880 | Completed Phase 1 DMC

• 1 other identifier: 1014425
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 3

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

Conditions

Pain Perception; Root Resorption; Rate of Orthodontic Tooth Movement; Biomarkers

Keywords

Orthodontic tooth movement; Root resorption; RANKL; Tooth alignment; Vitamin C; Vitamin E; Pain perception; Osteoprotegerin; RUNX2

Outcome Measures

Primary Outcomes (1)

• 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.

  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

  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

  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

  8 weeks after the start of treatment.

• Levels of biomarkers (RANKL, OPG, and RUNX2) in gingival crevicular fluid (GCF):

  Pre-treatment (T0), 1 week (T1), and 4 weeks (T2) after the start of treatment.

Study Arms (3)

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).

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).

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.

Other: Saline Solution (Control)

Interventions

1: Vitamin C Supplementation DRUG

• 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.

Arm 1: Vitamin C Treatment

Vitamin E Supplementation DRUG

• 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 concentration will be 60 mg in 0.4 ml, and the produced volume will be divided by six lower anterior teeth; each tooth will receive 0.07 ml (10 mg) of the vitamin E.

Vitamin E Treatment

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.

Arm 3: Saline Control

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• \. The overbite and overjet should not impede bracket placement on the mandibular anterior teeth.

You may not qualify if:

• 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.
• 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)

Sponsors & Collaborators

• University of Baghdad: lead

Study Sites (3)

Baghdad Al-Karkh Health Directorate, Baghdad, Iraq

Baghdad, Baghdad Governorate, 10013, Iraq

Location

Baghdad Al-Rusafa Health Directorate

Baghdad, Baghdad Governorate, 10061, Iraq

Location

College of Dentistry, University of Baghdad, Baghdad, Iraq

Baghdad, Baghdad Governorate, 10071, Iraq

Location

Related Publications (9)

• 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.

  PMID: 32908655 RESULT

• Yussif, 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.

  RESULT

• 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).

  RESULT

• 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.

  PMID: 38836668 RESULT

• Kappus 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.

  PMID: 1628854 RESULT

• Esenlik 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.

  PMID: 22113708 RESULT

• Carr 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.

  PMID: 32223303 RESULT

• Mucklow, J.C. (2000). Martindale: the complete drug reference. British journal of clinical pharmacology, 49(6), p.613.

  RESULT

• 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.

  PMID: 15817846 RESULT

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MeSH Terms

Conditions

Root Resorption

Interventions

Saline Solution

Condition Hierarchy (Ancestors)

Tooth Resorption; Tooth Diseases; Stomatognathic Diseases

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Professor Dr. Yassir Abdulkadhim Yassir, Ph.D. (Orthodontics) (UK)

  University of Baghdad

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: No additional parties are masked in this clinical trial beyond the participant, care provider, and outcomes assessor.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: 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).

Study Record Dates

• First Submitted: February 1, 2025
• First Posted: February 26, 2025
• Study Start: February 23, 2025
• Primary Completion: February 28, 2026
• Study Completion: February 28, 2026
• Last Updated: April 2, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

IR (3)