Effect of N-Acetylcysteine on Autologous Fat Graft Survival

Sponsor

Michael Bezuhly (Other)

Overall Status

Unknown status

CT.gov ID

NCT02788292

Collaborator

(none)

Enrollment

Arms

Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Adipose Tissue Atrophy Deformity of Reconstructed Breast Graft Loss	Drug: Acetylcysteine	Phase 4

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

14 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Effect of N-Acetylcysteine on Autologous Fat Graft Survival

Study Start Date :

Jul 1, 2016

Anticipated Primary Completion Date :

Dec 1, 2017

Anticipated Study Completion Date :

Jun 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Acetylcysteine (NAC) NAC added to tumescent solution for liposuction and eventual fat grafting.	Drug: Acetylcysteine See arm description Other Names: N-acetylcysteine
No Intervention: Control Just tumescent solution for liposuction and fat grafting.

Arm

Intervention/Treatment

Experimental: Acetylcysteine (NAC)

NAC added to tumescent solution for liposuction and eventual fat grafting.

Drug: Acetylcysteine

See arm description

Other Names:

N-acetylcysteine

No Intervention: Control

Just tumescent solution for liposuction and fat grafting.

Outcome Measures

Primary Outcome Measures

Change in fat graft volume over time [0, 1 and 3 months]
Based on CT scans of fat grafts and three-dimensional reconstructions/volumetric analysis

Secondary Outcome Measures

Weight of fat graft [3 months]
Fat grafts will be explanted and weighed at 3 months.
Fat graft vascularity [3 months]
Vascularity of fat graft with CD31 staining.
Fat graft quality [3 months]
Quality of fat graft through histological analysis of cysts/vacuoles/intact fat cells/fibrosis and also through adipocyte slide coverage analysis.
Adverse effects or complications [1 year]
Collecting data regarding any adverse complications of the fat grafting procedure and subsequent recovery.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 45 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

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

Exclusion Criteria:

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
Pregnancy or planned pregnancy within 1 year
Contraindications to CT
Previous hip/thigh surgery or injury
Previous lower leg surgery/injury
Smoker
Breastfeeding
Other disease according to investigator's judgment