Evaluation the Efficacy of Zinc on Botulinum Toxin A Injection (BTX-A)

November 25, 2025 updated by: Tishreen University

Evaluation of the Efficacy of Zinc on the Duration and Effictiveness of Botulinum Toxin A Injection in the Context of Hyperactive Masseter Muscle (A Prospective Clinical Study)

This clinical trial seeks to investigate a promising new approach to enhance the effectiveness and duration of Botulinum Toxin A (BTX-A) for the treatment of hyperactive masseter muscles. By investigating the role of oral zinc supplementation, this study could provide a cost-effective, sustainable solution for patients suffering from both aesthetic concerns and functional limitations associated with MMH and bruxism. The findings of this study will expand the clinical applications of BTX-A, offering longer-lasting relief and reducing the need for frequent injections, which could revolutionize the management of MMH in clinical practice.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

This study aims to explore the potential for oral zinc supplementation to enhance the efficacy and duration of Botulinum Toxin A (BTX-A) in treating hyperactive masseter muscles (MMH). MMH leads to cosmetic deformities like a "square jaw," and is sometimes associated with bruxism and functional issues. While BTX-A is effective for reducing muscle activity, its effects typically last 2-3 months, requiring frequent re-injections. The study hypothesizes that zinc supplementation, which plays a crucial role in synaptic transmission, may prolong and enhance the effects of BTX-A. The trial will be a randomized, double-blind, two-period design at Lattakia University Hospital, recruiting 20 participants aged 18-60 years, who will be randomly assigned to two treatment sequences.

The intervention protocol includes participants with a clinical diagnosis of MMH (with or without bruxism). They will undergo two separate treatment periods: one with zinc gluconate (50 mg/day for 4 days) followed by BTX-A injection, and the other with an identical placebo followed by the same BTX-A protocol. The two treatment periods will be separated by a 5-6 month washout period to eliminate carryover effects, ensuring that the results of the first treatment phase do not influence the second phase.

The primary outcome will be the percentage change in masseter electromyographic (EMG) amplitude at 12 weeks post-injection, compared with baseline (normalized to maximal voluntary clench [MVC]). This will provide data on the magnitude and duration of BTX-A's effect when combined with zinc supplementation. Secondary outcomes will include pain reduction (measured by the Visual Analog Scale [VAS]), patient satisfaction (assessed by a 5-point Likert scale), and time to recovery (time taken for EMG to return to 80% of baseline levels). Additionally, adverse events such as muscle weakness, asymmetry, and bruising will be monitored.

The results of this research could provide a cost-effective and sustainable solution for MMH patients, improving the duration and efficacy of BTX-A treatment.

Study Type

Interventional

Enrollment (Estimated)

20

Phase

  • Not Applicable

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 Backup

Study Locations

  • Syria
      • Latakia, Syria
        • lattakia university

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

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

Participants will be adults aged 18-60 years presenting with clinically confirmed masseteric hypertrophy or hyperactivity, as approved by EMG.

Exclusion Criteria:

  • Pregnancy or lactation;
  • Patients have aminoglycosides or vit B12.
  • Prior BTX-A treatment to the masseter within the previous 12 months;
  • Neuromuscular disorders or hypersensitivity to BTX-A or zinc compounds;
  • Systemic illness affecting zinc metabolism (e.g., hepatic, renal, or metabolic disorders);
  • Active infection, inflammation, or cutaneous lesions at the injection site.

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: Sequential Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Zinc arm
BTX-A Injection with Zinc
Drug: BOTOX 100U in normal saline with zinc

Pre-treatment (Period days -4 to -1)

• Zinc arm: Zinc gluconate 50 mg orally once daily for 4 days prior to injections.

BTX-A injections (Period day 0)

  • Agent: botulinum toxin A (BTX-A).
  • Target: Bilateral masseter muscles only.
  • Dose and mapping: 25-30 Units per side, delivered at 3 standardized points within the masseter safe zone. Mapping is guided by palpation at maximum voluntary clench (MVC) to identify the hypertrophic belly; injections are placed into the muscle belly, avoiding parotid duct and mandibular notch.

A washout interval of at least 5-6 months, or until the masseter EMG amplitude returns to ≥80% of baseline, will separate the two treatment phases to eliminate residual BTX-A effects and avoid carryover.

We reinject (BTX-A) to the same patient , but with a Placebo
Placebo Comparator: Placebo arm
BTX-A Injection with placebo
Drug: BOTOX 100U in normal saline with placebo

Pre-treatment (Period days -4 to -1)

• Placebo arm: Identical capsule orally once daily for 4 days prior to injections.

Adherence is reinforced with written instructions, dosing calendars, and pill counts.

BTX-A injections (Period day 0)

  • Agent: botulinum toxin A (BTX-A).
  • Target: Bilateral masseter muscles only.
  • Dose and mapping: 25-30 Units per side, delivered at 3 standardized points within the masseter safe zone. Mapping is guided by palpation at maximum voluntary clench (MVC) to identify the hypertrophic belly; injections are placed into the muscle belly, avoiding parotid duct and mandibular notch.

A washout interval of at least 5-6 months, or until the masseter EMG amplitude returns to ≥80% of baseline, will separate the two treatment phases to eliminate residual BTX-A effects and avoid carryover.

We reinject (BTX-A) to the same patient , but with zinc

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Primary Outcome
Time Frame: 12 weeks

• Percentage change in surface electromyographic (sEMG) amplitude of the masseter muscle at 12 weeks post-injection compared with baseline (normalized to maximal voluntary clench [MVC]).

This endpoint captures the magnitude and persistence of neuromuscular inhibition, corresponding to the clinically relevant window where BTX-A efficacy typically begins to wane.
12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Secondary Outcome
Time Frame: 12 weeks
• Patient satisfaction (5-point likert scale);
12 weeks

Collaborators and Investigators

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

Sponsor

Tishreen University

Investigators

  • Study Chair: Mohammad Asmi, lattakia university

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.

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 (Estimated)

December 1, 2025

Primary Completion (Estimated)

September 1, 2026

Study Completion (Estimated)

December 1, 2026

Study Registration Dates

First Submitted

November 18, 2025

First Submitted That Met QC Criteria

November 25, 2025

First Posted (Actual)

December 8, 2025

Study Record Updates

Last Update Posted (Actual)

December 8, 2025

Last Update Submitted That Met QC Criteria

November 25, 2025

Last Verified

November 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TishreenU maxilofacial surgery

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.

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