Head-to-Head Comparison of All Botulinum Neurotoxin Type A Products for Glabellar Rhytides

Wrinkle Clinical Trial

Official title:

Head-to-Head Comparison of the Efficacy and Safety of All Five Commercially Available Botulinum Neurotoxin Type A Products for the Treatment of Glabellar Rhytides: A Multicenter, Triple-Blind, Randomized Controlled Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06448676
• Other study ID #: 2024-514936-26-00
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: January 1, 2025
• Est. completion date: November 1, 2025

Study information

• Verified date: June 2024
• Source: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Contact: Serge A. Steenen, MD DMD
• Phone: +316 26 457 415
• Email: s.a.steenen[@]amsterdamumc.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Study Type: This is a multicenter, triple-blind, randomized controlled trial.

Purpose: The goal of this clinical trial is to compare the effectiveness and safety of all five commercially available Botulinum Neurotoxin Type A (BoNT-A) products for treating glabellar rhytides, commonly known as frown lines. This study is designed to provide comprehensive data on how these treatments compare in terms of improving frown lines and the duration of their effects.

Main Questions the Study Aims to Answer:

Which BoNT-A product provides the longest lasting effect on reducing glabellar rhytides? How do these products compare in terms of safety and the occurrence of side effects?

Participant Tasks:

Women aged 18 years or older with moderate to severe glabellar lines will participate.

Participants will receive injections of a BoNT-A product into specific facial muscles.

They will need to take weekly photographs using their smartphones to document changes in their frown lines.

These photos will be securely sent to our research team for analysis. Participants will complete questionnaires at the start and end of the study to assess their satisfaction, quality of life, and any changes in their condition.

Comparison Group:

Researchers will compare participants receiving different types of BoNT-A products to see which one is more effective at reducing frown lines and maintaining these effects over time.

The safety profiles of these products will also be compared to determine which has the fewest and least severe side effects.

This study aims to fill important gaps in our understanding of Botulinum Neurotoxin Type A treatments, guiding more effective clinical decisions and improving patient outcomes.

Description:

Background: Glabellar rhytides, commonly known as frown lines, are a significant aesthetic concern for many individuals, leading to increasing utilization of Botulinum Neurotoxin Type A (BoNT-A) treatments. Despite multiple products being available, comprehensive comparative data on their efficacy and safety are limited. This trial aims to fill this evidence gap by evaluating and comparing the effectiveness and safety profiles of all five FDA-approved BoNT-A products.

Methods: Conducted across several clinical sites, this multicenter, triple-blind, randomized controlled trial will involve a structured intervention where participants receive one of five different BoNT-A formulations. The study employs a stringent blinding and randomization process to ensure the objectivity and reliability of the results. Data on treatment efficacy, safety, and participant-reported outcomes will be collected at baseline and follow-up through direct clinical assessments and secure digital communication methods.

Data Collection and Analysis: Data collection will include baseline and 16-week follow-up assessments using standardized clinical scales and self-reported question anaires. Participants will document 30 weekly progress through standardized 'selfie' photos using a secure, encrypted application to ensure data privacy. The primary outcome, the duration of treatment efficacy, will be analyzed using Kaplan-Meier survival analysis. Secondary outcomes, including the incidence of adverse events and participant satisfaction, will be analyzed using repeated measures ANOVA and logistic regression. Detailed duration of effect will be assessed using Kaplan-Meier curves and Cox proportional hazards models.

Statistical Analysis: The study is powered to detect meaningful clinical differences between the treatment groups with a high degree of statistical confidence. The analysis will explore treatment effects over time and assess factors influencing treatment efficacy and safety.

Conclusion: By rigorously comparing all available BoNT-A products, this study will provide critical insights into their relative effectiveness and safety, significantly informing clinical decision-making and optimizing patient care strategies for treating glabellar lines. The findings are expected to enhance the understanding of treatment dynamics and guide future therapeutic approaches in aesthetic medicine.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 240
• Est. completion date: November 1, 2025
• Est. primary completion date: October 1, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Women aged 18 years or over, with moderate to severe glabellar lines

• Willing to provide written informed consent

• American Society of Anesthesiologists (ASA) Physical Status Classification 1 or 2

Exclusion Criteria:

• ASA Classification 3 or over

• History of hypersensitivity or adverse reactions to botulinum toxin or any of its components

• Infection at the injection site

• Previous treatment with botulinum toxin (lifetime)

• Pregnant or breastfeeding women

• Neuromuscular disorders or conditions that could interfere with the study assessments

Related Conditions & MeSH terms

• Wrinkle

Intervention

Drug:
• Botulinum toxin type A
Head-to-head comparison of all commercially available botulinum neurotoxin type A products

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)	Universitair Medical Centrum Groningen

References & Publications (19)

Bertucci V, Solish N, Kaufman-Janette J, Yoelin S, Shamban A, Schlessinger J, Snyder D, Gallagher C, Liu Y, Shears G, Rubio RG. DaxibotulinumtoxinA for Injection has a prolonged duration of response in the treatment of glabellar lines: Pooled data from two multicenter, randomized, double-blind, placebo-controlled, phase 3 studies (SAKURA 1 and SAKURA 2). J Am Acad Dermatol. 2020 Apr;82(4):838-845. doi: 10.1016/j.jaad.2019.06.1313. Epub 2019 Nov 29. — View Citation

Bohart Z, Dashtipour K, Kim H, Schwartz M, Zuzek A, Singh R, Nelson M. Real-world differences in dosing and clinical utilization of OnabotulinumtoxinA and AbobotulinumtoxinA in the treatment of upper limb spasticity. Toxicon. 2024 Apr;241:107678. doi: 10.1016/j.toxicon.2024.107678. Epub 2024 Mar 4. — View Citation

Dayan S, Joseph J, Moradi A, Lorenc ZP, Coleman K, Ablon G, Kaufman-Janette J, Cox SE, Campbell A, Munavalli G, Prygova I. Subject satisfaction and psychological well-being with escalating abobotulinumtoxinA injection dose for the treatment of moderate to severe glabellar lines. J Cosmet Dermatol. 2022 Jun;21(6):2407-2416. doi: 10.1111/jocd.14906. Epub 2022 Apr 12. — View Citation

Decates T, de Wijs L, Nijsten T, Velthuis P. Numbers on injectable treatments in the Netherlands in 2016. J Eur Acad Dermatol Venereol. 2018 Aug;32(8):e328-e330. doi: 10.1111/jdv.14877. Epub 2018 Mar 6. No abstract available. — View Citation

Decates TS, Velthuis P, Zarringam D, Bruin L, Schepers RH, van der Lei B. Upward trend in number of injectable treatments in the Netherlands 2016-2019. J Cosmet Dermatol. 2021 Sep;20(9):3049-3051. doi: 10.1111/jocd.14339. Epub 2021 Jul 19. No abstract available. — View Citation

Gostimir M, Liou V, Yoon MK. Safety of Botulinum Toxin A Injections for Facial Rejuvenation: A Meta-Analysis of 9,669 Patients. Ophthalmic Plast Reconstr Surg. 2023 Jan-Feb 01;39(1):13-25. doi: 10.1097/IOP.0000000000002169. Epub 2022 Mar 30. — View Citation

Honeck P, Weiss C, Sterry W, Rzany B; Gladys study group. Reproducibility of a four-point clinical severity score for glabellar frown lines. Br J Dermatol. 2003 Aug;149(2):306-10. doi: 10.1046/j.1365-2133.2003.05436.x. — View Citation

Jia Z, Lu H, Yang X, Jin X, Wu R, Zhao J, Chen L, Qi Z. Adverse Events of Botulinum Toxin Type A in Facial Rejuvenation: A Systematic Review and Meta-Analysis. Aesthetic Plast Surg. 2016 Oct;40(5):769-77. doi: 10.1007/s00266-016-0682-1. Epub 2016 Aug 5. — View Citation

Joseph J, Moradi A, Lorenc ZP, Coleman K, Ablon G, Kaufman-Janette J, Cox SE, Campbell A, Dayan S, Berg AK, Munavalli G. AbobotulinumtoxinA for the Treatment of Moderate-to-Severe Glabellar Lines: A Randomized, Dose-Escalating, Double-Blind Study. J Drugs Dermatol. 2021 Sep 1;20(9):980-987. doi: 10.36849/jdd.6263. — View Citation

Kerscher M, Fabi S, Fischer T, Gold M, Joseph J, Prager W, Rzany B, Yoelin S, Roll S, Klein G, Maas C. IncobotulinumtoxinA Demonstrates Safety and Prolonged Duration of Effect in a Dose-Ranging Study for Glabellar Lines. J Drugs Dermatol. 2021 Oct 1;20(10):1052-1060. doi: 10.36849/JDD.6377. — View Citation

Li X, Sui C, Xia X, Chen X. Efficacy and Safety of Botulinum Toxin Type A for Treatment of Glabellar Lines: A Network Meta-Analysis of Randomized Controlled Trials. Aesthetic Plast Surg. 2023 Feb;47(1):365-377. doi: 10.1007/s00266-022-03018-y. Epub 2022 Sep 12. — View Citation

Lorenc ZP, Adelglass JM, Avelar RL, Baumann L, Beer KR, Cohen JL, Cox SE, Dayan SH, Dover JS, Downie JB, Draelos ZD, Goldman MP, Gross JE, Joseph JH, Kaufman-Janette J, Moy RL, Nestor M, Schlessinger J, Smith SR, Weiss RA. The Second of Two One-Year, Multicenter, Open-Label, Repeat-Dose, Phase II Safety Studies of PrabotulinumtoxinA for the Treatment of Moderate to Severe Glabellar Lines in Adult Patients. Aesthet Surg J. 2021 Nov 12;41(12):1423-1438. doi: 10.1093/asj/sjaa382. Erratum In: Aesthet Surg J. 2021 Jun 30;: — View Citation

Polacco MA, Singleton AE, Barnes CH, Maas C, Maas CS. A Double-Blind, Randomized Clinical Trial to Determine Effects of Increasing Doses and Dose-Response Relationship of IncobotulinumtoxinA in the Treatment of Glabellar Rhytids. Aesthet Surg J. 2021 May 18;41(6):NP500-NP511. doi: 10.1093/asj/sjaa220. — View Citation

Shome D, Kapoor R, Khare S. Two different types of botulinum toxins: Is there a difference in efficacy and longevity? J Cosmet Dermatol. 2019 Dec;18(6):1635-1641. doi: 10.1111/jocd.12949. Epub 2019 May 28. — View Citation

Steenen SA, Bauland CG, de Lange J, van der Lei B. Complications After Botulinum Neurotoxin Type A and Dermal Filler Injections: Data From a Large Retrospective Cohort Study. Aesthet Surg J. 2023 Jan 9;43(1):NP56-NP63. doi: 10.1093/asj/sjac228. No abstract available. — View Citation

Steenen SA, Bauland CG, van der Lei B, Su N, van Engelen MDG, Anandbahadoer-Sitaldin RDRRAL, Koeiman W, Jawidan T, Hamraz Y, Lange J. Head-to-head comparison of 4 hyaluronic acid dermal fillers for lip augmentation: A multicenter randomized, quadruple-blind, controlled clinical trial. J Am Acad Dermatol. 2023 Apr;88(4):932-935. doi: 10.1016/j.jaad.2022.11.012. Epub 2022 Nov 9. No abstract available. — View Citation

Taylor SC, Grimes PE, Joseph JH, Jonker A, Avelar RL. PrabotulinumtoxinA for the Treatment of Moderate-to-Severe Glabellar Lines in Adult Patients With Skin of Color: Post Hoc Analyses of the US Phase III Clinical Study Data. Dermatol Surg. 2021 Apr 1;47(4):516-521. doi: 10.1097/DSS.0000000000002864. — View Citation

Zargaran D, Zoller F, Zargaran A, Rahman E, Woollard A, Weyrich T, Mosahebi A. Complications of Cosmetic Botulinum Toxin A Injections to the Upper Face: A Systematic Review and Meta-Analysis. Aesthet Surg J. 2022 Apr 12;42(5):NP327-NP336. doi: 10.1093/asj/sjac036. — View Citation

Zargaran D, Zoller FE, Zargaran A, Mosahebi A. Complications of facial cosmetic botulinum toxin A injection: analysis of the UK Medicines & Healthcare Products Regulatory Agency registry and literature review. J Plast Reconstr Aesthet Surg. 2022 Jan;75(1):392-401. doi: 10.1016/j.bjps.2021.05.074. Epub 2021 Jun 17. — View Citation

* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Duration of Clinical Efficacy	Period until loss of treatment effect, measured as the percentage of participants who maintain at least a 1-point improvement in glabellar line severity at maximum frown from baseline to week 16, assessed using the "four-point clinical severity score for glabellar frown lines" developed by Honeck.	From baseline to week 16
Secondary	Duration of Clinical Efficacy	Median time to loss of effect	Kaplan-Meier survival curves and Cox proportional hazards models to analyze the time to complete loss of effect across the entire study duration (From baseline to week 30)
Secondary	Incidence of Adverse Events (AEs)	Occurrences of adverse events such as ptosis, strabismus, and eyelid sensory disorders throughout the study period	From baseline to week 16
Secondary	Quality of Life (FACE-Q)	FACE-Q Psychological Wellbeing Scores, (values 10-40), higher score means a better outcome	From baseline to week 16
Secondary	Social Functioning (FACE-Q)	FACE-Q Social Scores, (values 8-32), higher score means a better outcome	From baseline to week 16
Secondary	Satisfaction with the Result (FACE-Q)	FACE-Q Outcome Scores, (values 6-24), higher score means a better outcome	From baseline to week 16
Secondary	Depressive Symptoms	Hospital Anxiety and Depression Scale (HADS) Depression Scores, (values 0-21), higher score means a worse outcome	Baseline to week 4
Secondary	Anxiety Symptoms	Hospital Anxiety and Depression Scale (HADS) Anxiety Scores, (values 0-21), higher score means a worse outcome	Baseline to week 4
Secondary	Migraine Symptoms	Migraine Disability Assessment (MIDAS) Scores, (values 0-21+), higher score means a worse outcome	Baseline to week 4
Secondary	Headache Symptoms	Headache Impact Test (HIT-6) Scores, (values 36-78), higher score means a worse outcome	Baseline to week 4
Secondary	Side Effects (FACE-Q)	FACE-Q Early Life Impact Scores, (values 17-68), higher score means a worse outcome	First 2 weeks after treatment