Clinical trial NCT02788292: Effect of N-Acetylcysteine on Autologous Fat Graft Survival
Official title: Effect of N-Acetylcysteine on Autologous Fat Graft Survival
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE4
Conditions: Adipose Tissue Atrophy
Deformity of Reconstructed Breast
Graft Loss
Keywords: acetylcysteine
three-dimensional reconstruction
autologous fat grafting
Lead sponsor: Nova Scotia Health Authority
Sponsor class: OTHER
First posted: 2016-06-02
Enrollment: 0
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A single-centre triple-blind study looking at the addition of NAC to tumescent solution for liposuction and fat grafting in healthy patient volunteers already undergoing bilateral breast reduction. Three-dimensional reconstructions and volumetric analysis will be performed based on CT scans at 0, 1 and 3 months and then histological analysis will be performed after fat graft explantation at 3 months to determine fat graft vascularity and quality.

Detailed description: Autologous fat grafting is an increasingly popular technique for soft tissue reconstruction; however, the surgical technique is limited by inconsistent graft take, undercorrection, and requirement for repeat procedures. The authors previously examined whether a widely available, clinically safe anti-oxidant, N-acetylcysteine (NAC), could improve adipose-derived stem cell survival and subsequent graft take when added to tumescent solution at the time of fat harvest in mice. The addition of NAC to tumescent fluid during fat harvest in mice protects ADSCs against oxidative stress, increases their survival and proliferation, and inhibits their early differentiation into mature adipocytes in vitro. In an in vivo model, NAC treatment at the time of harvest improved survival and quality of autologous fat grafts. These observations provide proof-of-principle for the use of NAC in the clinical setting to optimize fat graft yields.

Hypothesis: The addition of NAC to the tumescent solution used in fat grafting will improve fat graft survival in humans to potentially decrease the amount of re-operations and undercorrection that occurs.

Plan: The study will be conducted as a single-centre, randomized, triple-blind placebo-controlled trial to be performed at the QEII Health Sciences Centre, Halifax, Nova Scotia. Subjects will be chosen as healthy female patients already presenting to the operating room for elective breast reduction surgery. These patients will be enrolled and booked for surgery as they present to clinic and will not be expedited in receiving their elective surgery if enrolled in the study. Each subject will serve as her own control. The hypothesis will be tested by performing lipoaspiration of the thigh/hip region of healthy patients after the addition of tumescent solution with or without NAC. Approximately 10 millilitres of the fat graft will be injected into each pre-tibial area depending on the randomization allocation, as described by Kolle et al. (1) The volume of fat graft will be measured at 0, 1 and 3 months using computed tomographic (CT) scans according to institutional standards. The CT images will be exported into Materialise Interactive Medical Image Control System (MIMICS) and volumetric three-dimensional reconstructions will be made to measure the size and volume of the grafts at each of the time points. The grafts will then be explanted at 3 months and weighed. The histologic appearance, graded on the amount of inflammation, cysts/vacuoles, integrity and vascularity with CD31 staining will be assessed. The results will be compared using two-tailed t-tests. Statistical significance will be set at p\<0.05.

Eligibility criteria: Inclusion Criteria:

1. Women
2. Desire and surgical indication for liposuction of the thigh/hip region for women already undergoing elective breast reduction surgery
3. Age 18-45 years
4. BMI of 20-30
5. ASA Class I

Exclusion Criteria:

1. Known chronic illnesses: Diabetes, HIV, renal/liver failure, metabolic disease, history of cancer or family pre-disposition of cancer, peripheral vascular disease, illness that would preclude a general anaesthetic
2. Pregnancy or planned pregnancy within 1 year
3. Contraindications to CT
4. Previous hip/thigh surgery or injury
5. Previous lower leg surgery/injury
6. Smoker
7. Breastfeeding
8. Other disease according to investigator's judgment

Primary outcomes:
measure: Change in fat graft volume over time
timeFrame: 0, 1 and 3 months
Secondary outcomes:
measure: Weight of fat graft
timeFrame: 3 months
measure: Fat graft vascularity
timeFrame: 3 months
measure: Fat graft quality
timeFrame: 3 months
measure: Adverse effects or complications
timeFrame: 1 year
Other outcomes:
Locations:
Study officials:
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