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WrinklePhase 4NCT06448676

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

A Phase 4 study testing Botulinum toxin type A in people with Wrinkle and Glabellar Frown Lines, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 3 sites in Netherlands.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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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 commercially available Botulinum Neurotoxin Type A (BoNT-A) products for treating glabellar rhytides, commonly known as frown lines. Read more about this study

Who is it for?
Ages 18 years and older, women onlyHealthy volunteers can take part
What is being tested?
Botulinum toxin type A
Could I receive a placebo?
No, everyone receives an active treatment
How many people
325 participants
Where
3 sitesNetherlands
Study dates
2 Feb 2026to 1 Feb 2027
Phase
Phase 4
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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
  • Negative pregnancy test

Who cannot join

  • 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

Trial locations and contacts

3 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Serge A. Steenen, MD DMD contact

+316 26 457 415

s.a.steenen@amsterdamumc.nl

Netherlands3 sites, 3 recruiting

  • Faceland

    Amsterdam

    Dr. Murielle van Engelen, MD, +31881014600

    Recruiting

  • Faceland

    Eindhoven

    Dr. Whitney Koeiman, MD, +31881014600

    Recruiting

  • Faceland

    Utrecht

    Dr. Steenen, MD DMD, +31881014600

    Recruiting

Other trials in Netherlands

About this study

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, Double-Blind, Randomized Controlled Trial

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 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.

Read more

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.

Read the detailed 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, double-blind, randomized controlled trial will involve a structured intervention where participants receive one of the 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.

Being tested
Botulinum toxin type A

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Botulinum toxin type ADrug

    Head-to-head comparison of all commercially available botulinum neurotoxin type A products

Study groups in NCT06448676
Study groupRoleWhat they receive
OnabotulinumtoxinA: 20 unitsActive comparator20 units (4-4-4-4-4) Commercial Name: Botox® Producing Company: Allergan, an AbbVie company Location: Dublin, Ireland Additional Commercial Names: Vistabel® (in some regions, especially Europe)
Receives: Drug: Botulinum toxin type A
IncobotulinumtoxinA: 20 unitsActive comparator20 units (4-4-4-4-4) Commercial Name: Xeomin® Producing Company: Merz Pharmaceuticals Location: Frankfurt, Germany Additional Commercial Names: Bocouture® (for aesthetic use in some regions)
Receives: Drug: Botulinum toxin type A
AbobotulinumtoxinA: 50 (Speywood) unitsActive comparator50 units (10-10-10-10-10) Commercial Name: Dysport® Producing Company: Ipsen Biopharmaceuticals, Inc. Location: Paris, France Additional Commercial Names: Azzalure® (for aesthetic use in some regions)
Receives: Drug: Botulinum toxin type A
AbobotulinumtoxinA: 60 (Speywood) unitsActive comparator60 units (12-12-12-12-12) Commercial Name: Dysport® Producing Company: Ipsen Biopharmaceuticals, Inc. Location: Paris, France Additional Commercial Names: Azzalure® (for aesthetic use in some regions)
Receives: Drug: Botulinum toxin type A
PrabotulinumtoxinA 20 unitsActive comparator20 units (4-4-4-4-4) Commercial Name: Jeuveau® Producing Company: Evolus, Inc. Location: Newport Beach, California, USA Additional Commercial Names: Nuceiva® (for aesthetic use in some regions)
Receives: Drug: Botulinum toxin type A

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: From baseline to week 16

Secondary outcomes (10)

  1. Duration of Clinical Efficacy

    Median time to loss of effect

    Measured: 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)

  2. Incidence of Adverse Events (AEs)

    Occurrences of adverse events such as ptosis, strabismus, and eyelid sensory disorders throughout the study period

    Measured: From baseline to week 16

  3. Quality of Life (FACE-Q)

    FACE-Q Psychological Wellbeing Scores, (values 10-40), higher score means a better outcome

    Measured: From baseline to week 16

  4. Social Functioning (FACE-Q)

    FACE-Q Social Scores, (values 8-32), higher score means a better outcome

    Measured: From baseline to week 16

  5. Satisfaction with the Result (FACE-Q)

    FACE-Q Outcome Scores, (values 6-24), higher score means a better outcome

    Measured: From baseline to week 16

  6. Depressive Symptoms

    Hospital Anxiety and Depression Scale (HADS) Depression Scores, (values 0-21), higher score means a worse outcome

    Measured: Baseline to week 4

  7. Anxiety Symptoms

    Hospital Anxiety and Depression Scale (HADS) Anxiety Scores, (values 0-21), higher score means a worse outcome

    Measured: Baseline to week 4

  8. Migraine Symptoms

    Migraine Disability Assessment (MIDAS) Scores, (values 0-21+), higher score means a worse outcome

    Measured: Baseline to week 4

  9. Headache Symptoms

    Headache Impact Test (HIT-6) Scores, (values 36-78), higher score means a worse outcome

    Measured: Baseline to week 4

  10. Side Effects (FACE-Q)

    FACE-Q Early Life Impact Scores, (values 17-68), higher score means a worse outcome

    Measured: First 2 weeks after treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Jun 2024
  2. Study start2 Feb 2026
  3. Primary completion15 Jan 2027 (estimated)
  4. Study completion1 Feb 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
This study is a double-blind, multi-center, parallel-group randomized controlled trial designed to compare the efficacy and safety of onabotulinumtoxinA, abobotulinumtoxinA, incobotulinumtoxinA, and prabotulinumtoxinA, for the treatment of glabellar rhytides.
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
325 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06448676
Sponsor's protocol ID
2024-514936-26-00
Status last verified
Aug 2026
First submitted
3 Jun 2024
Last updated
14 Aug 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 29444367

  • 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.

    PubMed 34403196

  • 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.

    PubMed 35953448

  • 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.

    PubMed 27495260

  • 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.

    PubMed 34456155

  • 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.

    PubMed 35353777

  • 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.

    PubMed 35178552

  • 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.

    PubMed 36097079

  • 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.

    PubMed 34636520

  • 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.

    PubMed 32722793

  • 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.

    PubMed 34491016

  • 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.

    PubMed 33944913

  • 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.

    PubMed 33165078

  • 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.

    PubMed 35266281

  • 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.

    PubMed 31791824

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Botulinum toxin type A in people with Wrinkle and Glabellar Frown Lines, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 3 sites in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 14 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Serge A. Steenen, MD DMD (+316 26 457 415, s.a.steenen@amsterdamumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Duration of Clinical Efficacy (time frame: From baseline to week 16). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06448676, which also lists 19 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Aug 2026.

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