Clinical trial NCT06847880: The Potential Effect of the Local Administration of Vitamins C and E on Orthodontic Treatment: a Randomized Clinical Trial
Official title: The Potential Effect of the Local Administration of Vitamins C and E on Orthodontic Treatment: a Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
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
Lead sponsor: University of Baghdad
Sponsor class: OTHER
First posted: 2025-02-26
Enrollment: 51
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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).
Primary purpose: TREATMENT

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. 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 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-blinded, parallel-group design with equal randomization (1:1) and is conducted in private clinics and hospitals.

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 Visual Analog Scale (VAS) during the first week after each archwire change.
* 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 severe mandibular anterior crowding (Little's Irregularity Index \[LII\] of 4-9 mm). 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:

1. Control Group: Receives saline injection.
2. Vitamin C Group: Receives intraepidermal injection of vitamin C (120 mg in 1.2 ml, divided among six mandibular anterior teeth).
3. Vitamin E Group: Receives intraepidermal injection of vitamin E (60 mg in 0.4 ml, divided among six mandibular anterior teeth).

Injections are repeated biweekly for a total of six months (24 weeks).

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 heat-activated nickel-titanium (HANT) archwires in the following sequence:

* 0.014-inch HANT (initial 4 weeks)
* 0.016-inch HANT (weeks 4-8)
* 0.018-inch HANT (weeks 8-24)

No additional orthodontic interventions, such as interproximal reduction or extractions, will be performed during the study period.

Data Collection and Outcome Assessments

Data will be collected at multiple time points throughout the study:

1. Mandibular Incisor Crowding Relief

   * 3D-scanned digital models will be used to measure Little's Irregularity Index (LII) at baseline and every 4 weeks until week 24.
2. Root Resorption

   * Standardized periapical radiographs of mandibular anterior teeth will be taken at baseline, 8 weeks, and 24 weeks to evaluate root resorption.
3. Pain Perception

   * Participants will record pain intensity on a VAS scale (0-10) during the first week after each wire change (every 4 weeks).
4. Patient Perception

   * A structured questionnaire assessing comfort, esthetics, and perceived treatment progress 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 v26.Statistical methods include:

* Descriptive statistics (mean, standard deviation, frequency).
* Reliability analysis for measurement consistency.
* Inferential statistics, including paired and independent t-tests, analysis of variance (ANOVA), and regression models, to compare treatment effects.

A significance level of 0.05 will be used for hypothesis testing.

Study Oversight and Ethical Considerations

The study is self-funded and complies with ethical guidelines for human research. Ethical approval is pending from the appropriate review board. All participants (or their legal guardians) will provide informed consent before enrollment.

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.

Eligibility criteria: Inclusion Criteria:

1. Patients aged 12 years and above, who are indicated for fixed appliance orthodontic treatment.
2. Patients with moderate to severe crowding (4-9 mm) of the mandibular anterior teeth as per the Little's Irregularity Index (LII).
3. 4. 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 or greater than 9 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)

Primary outcomes:
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
timeFrame: 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:
measure: Pain Perception After Archwire Placement: A Visual Analog Scale Assessment
timeFrame: From the placement of each archwire to 7 days post-placement.
measure: Amount of orthodontically-induced inflammatory root resorption (OIIRR) in the apical region of mandibular anterior teeth
timeFrame: Pre-treatment (T0), 8 weeks (T1), and 24 weeks (T2) after the start of treatment.
measure: Patient perception using a newly developed questionnaire for adjunctive orthodontic therapy
timeFrame: 8 weeks after the start of treatment.
measure: Levels of biomarkers (RANKL, OPG, and RUNX2) in gingival crevicular fluid (GCF):
timeFrame: Pre-treatment (T0), 1 week (T1), and 4 weeks (T2) after the start of treatment.
Other outcomes:
Locations:
city: Baghdad
country: Iraq
facility: Baghdad Al-Karkh Health Directorate, Baghdad, Iraq
city: Baghdad
country: Iraq
facility: Baghdad Al-Rusafa Health Directorate
city: Baghdad
country: Iraq
facility: College of Dentistry, University of Baghdad, Baghdad, Iraq
Study officials:
affiliation: University of Baghdad
name: Professor Dr. Yassir Abdulkadhim Yassir, Ph.D. (Orthodontics) (UK)
role: STUDY_DIRECTOR
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