Clinical trial NCT07008339: Impact of Nipple Reconstruction in Mastectomized Patients Using Cross-Linked Hyaluronic Acid Injection.
Official title: Impact of Nipple Reconstruction in Mastectomized Patients Using Cross-Linked Hyaluronic Acid Injection.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Breast Neoplasms
Mastectomy
Mammaplasty
Nipple Disorder
Tattooing
Hyaluronic Acid
Dermal Fillers
Reconstructive Surgical Procedures
Quality of Life
Self Concept
Body Image
Patient Satisfaction
Breast Reconstruction
Nipple Reconstruction
Keywords: Breast Cancer
Mastectomy
Breast Reconstruction
Nipple-Areola Complex Reconstruction
Nipple Reconstruction
Areola Reconstruction
Hyaluronic Acid
Dermal Fillers
Micropigmentation
Tattooing
Body Image
Quality of Life
Postmastectomy Reconstruction
Cross-linked Hyaluronic Acid
Patient Satisfaction
Breast Cancer Survivors
Lead sponsor: Germans Trias i Pujol Hospital
Sponsor class: OTHER
First posted: 2025-06-06
Enrollment: 138
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Mixed-methods study with a sequential explanatory design. Phase 1: Quantitative methodology. A parallel, randomized clinical trial developed based on the following hypothesis: nipple reconstruction using hyaluronic acid injection and micropigmentation increases satisfaction and quality of life in mastectomized patients.

Phase 2: Qualitative methodology. Constructivist paradigm. Descriptive phenomenological study.

The study will be conducted at the Areolar Micropigmentation Unit (UMA) of Germans Trias i Pujol University Hospital, a high-technology public hospital in the province of Barcelona, serving a local population of 250,000 and acting as a referral center for over 800,000 people. The UMA, part of the Breast Pathology Service and collaborating with the Plastic Surgery Department, treats an average of 53 patients per year and is staffed by two nurses specialized in Body Image and Dermoaesthetics.
Primary purpose: TREATMENT

Brief summary: This study evaluates the impact of hyaluronic acid (HA) injection for nipple projection following mastectomy, as a complement to areola micropigmentation. While micropigmentation is standard in nipple-areola complex (NAC) reconstruction, HA use remains novel, with limited data on psychosocial, sexual, and aesthetic outcomes.

A sequential explanatory mixed-methods design will be used. In Phase 1, a randomized controlled trial will compare two groups: one receiving NAC micropigmentation alone (control) and the other receiving micropigmentation plus HA-based nipple projection (intervention). A total of 138 participants will be recruited at the Areolar Micropigmentation Unit of Germans Trias i Pujol University Hospital (Barcelona) over 36 months. Outcomes will include psychosocial and sexual well-being, satisfaction with breast and nipple appearance, and nipple projection, measured using the Spanish BREAST-Q, a custom satisfaction tool, and calipers.

Phase 2 will involve a qualitative phenomenological study using semi-structured interviews with a purposive sample from the intervention group. Thematic analysis will explore body image, emotional and social well-being, and overall satisfaction, using NVivo software.

This is the first study assessing HA nipple reconstruction by advanced practice nurses using validated patient-reported outcomes. While the BREAST-Q is appropriate, it may not fully capture emotional nuances, justifying qualitative exploration. HA durability is estimated at 6-9 months, but residual volume and satisfaction over time remain underexplored. HA's aesthetic footprint may allow reduced dosages in future applications.

This minimally invasive technique may reduce the need for surgical nipple reconstruction. Conducting the procedure in a nurse-led setting is novel and may enhance patient-centered care and the role of nursing in post-mastectomy recovery.

The study complies with the Declaration of Helsinki and Spanish biomedical regulations. Ethical approval was obtained. Participants will provide informed consent, and data will be anonymized and securely stored.

Detailed description: Breast cancer is the most common malignant neoplasm among women worldwide. Similarly, in Spain, it is also the most prevalent tumor in women, surpassing colorectal cancer. The incidence of this disease in our country has steadily increased over the past decades, with approximately 26,000 cases diagnosed each year, accounting for 25-30% of all female malignancies. For affected individuals, both the disease and its treatment lead to physical and bodily changes, which in turn have significant emotional implications. A woman facing a breast cancer diagnosis and its associated management goes through a critical period in her life. During this time, the altered self-image resulting from various treatment side effects is often accompanied by a fear of losing femininity and self-confidence, with potentially significant repercussions on the patient's quality of life.

Modern society increasingly demands not only the cure of diseases but also the consideration of factors that enhance patients' quality of life. According to data from the Spanish Society of Plastic, Reconstructive and Aesthetic Surgery (SECPRE), of the 36,000 women mentioned above, approximately 64% will require a mastectomy-defined as the surgical removal of the entire affected breast-and 28% will undergo breast reconstruction.

For these women, the final stage of breast reconstruction typically culminates in the reconstruction of the nipple-areola complex (NAC), which, according to DiCenso et al., represents the conclusion of surgical and adjuvant treatments, as well as the end of uncertainty. It symbolizes the transition from patient to survivor. The healing process is not considered complete until the areola and nipple are reconstructed, thus achieving a morphologically complete breast rather than merely restoring volume.

Micropigmentation is a technique involving the deposition of pigment into the skin using ultra-fine needles. It is simple, safe, does not require general anesthesia, and can be performed by trained nurses in outpatient settings. When a neo-nipple has not been created or has retracted, subcutaneous injection of cross-linked hyaluronic acid (HA) can restore lost volume, improve the realism of micropigmentation, and support emotional healing by improving body image and self-esteem. HA is safe, hydrophilic, biocompatible, and widely used in dermal fillers for volume projection.

This study aims to evaluate the impact of HA-based nipple reconstruction in terms of psychosocial and sexual well-being, satisfaction with the breasts and nipples, and the patient's lived experience.

Specific objectives include:

Identifying the sociodemographic and clinical characteristics of the participants.

Assessing differences in psychosocial and sexual well-being, satisfaction with breasts, nipples, and micropigmentation.

Determining nipple projection and HA retention.

Exploring patient experiences with quality of life, self-confidence, and emotional recovery.

Study Design:

This is a mixed-methods study employing a sequential explanatory design. Phase 1 is a randomized controlled trial comparing micropigmentation alone (control) with micropigmentation plus HA injection (intervention). Phase 2 is a descriptive phenomenological study using semi-structured interviews and thematic analysis.

Setting:

Conducted at the Areolar Micropigmentation Unit, Germans Trias i Pujol University Hospital in Barcelona, a high-tech center that treats 53 patients yearly and is staffed by nurses trained in body image and dermoesthetics.

Population:

Women ≥18 undergoing NAC micropigmentation for the first time. Exclusion criteria include HA allergy or intolerance. Sample size: 138 women (69 per group) in Phase 1. Phase 2 will continue until data saturation (typically 5-15 participants).

Measurements:

BREAST-Q (Spanish version) will assess well-being and satisfaction. A custom questionnaire will assess satisfaction with micropigmentation. Nipple projection will be measured with calipers, and HA data recorded. Interviews will explore body image, self-esteem, intimacy, and expectations.

Data Collection:

Patients will be enrolled during UMA visits. After consent, baseline data and BREAST-Q will be collected. Micropigmentation will be done in 2-4 sessions. For the intervention group, HA will be administered 15 days post-micropigmentation in 2-3 dermal injections. Follow-ups include questionnaires post-procedure and at 3 and 6 months.

Analysis:

Quantitative data will be analyzed using SPSS v.29 with descriptive and inferential statistics (t-test, ANOVA, Mann-Whitney U, chi-square). Qualitative data will be analyzed using Braun \& Clarke's method in NVivo. Trustworthiness will be ensured by Lincoln \& Guba's criteria.

Limitations:

Challenges include lack of double-blinding, variable timelines, and emotional vulnerability. Measures include standardized protocols and extended data collection.

Justification:

This is the first study to evaluate HA-based nipple reconstruction performed by advanced practice nurses using validated PROMs. HA offers a minimally invasive, adjustable alternative to surgery with fewer complications. Its application in nurse-led outpatient care is novel.

Ethics:

Approved by the Ethics Committee of Germans Trias i Pujol Hospital. Conducted in compliance with the Declaration of Helsinki, Spanish biomedical regulations, and data protection laws (LOPD 3/2018). Informed consent will be obtained. Data will be pseudonymized and securely stored.

Eligibility criteria: * Quantitative Phase
* Inclusion Criteria:

Women over 18 years of age, or with parental or legal guardian consent.

At least one of the following criteria:

Women undergoing their first nipple-areola complex (NAC) reconstruction through micropigmentation and/or:

No previous neo-nipple surgery, either unilaterally or bilaterally.

Surgical reconstruction of the areola.

Surgical reconstruction of the NAC with subsequent retraction of the neo-nipple.

More than 6 months since their last surgery.

- Exclusion Criteria:

Allergy to hyaluronic acid.

Poor tolerance to needle injections.

Withdrawal Criteria:

Participant's voluntary decision.

Complications associated with the technique (allergy, hematoma, etc.).

Clinical deterioration preventing the woman from continuing in the study.

- Qualitative Phase

Participant Profile Characteristics: For the qualitative phase, women who have received NAC reconstruction with HA will be invited to participate, following the maximum variation criterion. To ensure the inclusion of participants with diverse characteristics and capture a wide range of perspectives and experiences on the phenomenon under study, women of varying ages, with different breast cancer diagnoses, and histories of various oncological, surgical, and therapeutic treatments will be selected.

Primary outcomes:
measure: Satisfaction with Nipple Reconstruction
timeFrame: 3, and 6 months after final injection session
Secondary outcomes:
measure: Psychosocial Well-being
timeFrame: Baseline, 3 months, and 6 months post-intervention
measure: Sexual Well-being
timeFrame: Baseline, 3 months, and 6 months post-intervention
measure: Satisfaction with Breasts
timeFrame: Baseline, 3 months, and 6 months post-intervention
measure: Satisfaction with Micropigmentation
timeFrame: Periprocedural
measure: Nipple Projection
timeFrame: Immediately post-procedure, 3 months, and 6 months
measure: Retention of Hyaluronic Acid
timeFrame: 3 and 6 months post-injection
Other outcomes:
Locations:
city: Badalona
country: Spain
facility: Hospital Universitario Germans Trias i Pujol
state: Barcelona
Study officials:
affiliation: Germans Trias i Pujol Hospital
name: Ariadna Huertas Zurriaga, RN
role: STUDY_DIRECTOR
affiliation: University of Barcelona
name: Sergio Alonso Fernández, RN
role: STUDY_DIRECTOR
affiliation: Universitat de Lleida
name: Joan Blanco Blanco, RN
role: STUDY_DIRECTOR
affiliation: Germans Trias i Pujol Hospital
name: Isabel Granados Navarrete, RN
role: PRINCIPAL_INVESTIGATOR
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