Safety Of Fat Micrografts With Adipose-Derived Stromal Vascular Fraction In Hands Of Patients With Systemic Sclerosis

Lipograft Safety Enriched With Vascular Stromal Fraction Derived From Adipose Tissue, to Treatment of Digital Joint Fibrosis and Refractory Ischemic Digital Ulcers Caused by Systemic Sclerosis

Systemic sclerosis (SS) causes microvascular alteration in the hand and subsequently pain, skin fibrosis, and osteoarticular deformities. These injuries initiate functional decline of the hand and decrease patient quality of life.

Local application of adipose-derived stromal vascular fraction (ADSVF) has been proposed as an emerging treatment. There are reports about the good results obtained after ADSVF treatment in this kind of patients. For these reasons , we aimed to evaluate the safety and clinical effect of application of fat micrografts enriched with ADSVF to the hands of patients with SS.

Study Overview

• Status: Completed
• Conditions: Systemic Sclerosis
• Intervention / Treatment: Drug: ADSVF application in the right hand

Detailed Description

The regenerative properties of adipose stem cells (ASCs) existing in the mixed cell fraction obtained by enzymatic digestion of adipose tissue, termed adipose-derived stromal vascular fraction (ADSVF), were initially described in 2002. These cells have the characteristics of being multipotent and exerting local angiogenic, anti-inflammatory, antifibrotic, immunomodulatory, and regenerative effects after application. ASCs express their angiogenic properties most effectively in a hypoxic environment.

For the above reasons, and because of its abundance in fat, easy acquisition, and almost immediate availability for use, ADSVF has positioned itself as an alternative for repair and regeneration of ischemic tissue.

Application of decanted fat, centrifuged fat, and ADSVF, has consistently and significantly improved pain, Raynaund Phenomen, and healing of digital ulcers in the hands of patients with SS, and thus improved their quality of life. Other inconsistent benefits have also been reported, such as decreased digital circumference, improvement in digital mobility and strength, improvement in formation of new subungual capillaries, and improvement in function through evaluation of the Cochin scale.

Based on the above findings, and because changes in the hands of patients with SS may arise through loss of adipocytes and defective stem cell function, we designed the present study with the aim of evaluating the safety, reproducibility, and clinical effects of application of fat micrografts enriched with ADSVF to the hands of patients affected with SS in a controlled clinical trial.

The experimental and control groups each contained 10 patients diagnosed with SS according to the criteria of the American College of Rheumatology and the LeRoy-Medsger criteria.

It was decided to carry out the treatment on the most affected hand of the patients, which was the right hand in the entire experimental group. ADSVF-enriched fat micrografts were applied to the experimental group. Evolution and medical therapy effects were observed in the control group.

The fat was obtained by liposucction and the ADSVF was processed in laboratory.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• Mexico
  • Mexico, Mexico, 14080
    • Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients diagnosed with SS, according to the criteria of the American College of Rheumatology and those of LeRoy-Medsger.
• Over 18 years old,
• BMI> 18 kg / m2.
• Patients received stable vasoactive and immunosuppressive therapies, for at least 1 month before being enrolled in the study, and this was continued unchanged throughout the study.

Exclusion Criteria:

• infected digital ulcers
• comorbidities that could affect hand function
• alcoholism
• drug abuse
• history of family cancer
• Patients with hyperbaric therapy one month before
• Botulinum toxin one month before
• surgical sympathectomy one month before

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Experimental group; 40 ml of fat was mixed with 2 ml of ADSVF and placed in 1-ml and 3-ml syringes. Using a 19-gauge blunt cannula (0.8 mm), 0.5 ml was applied to the radial and ulnar edge of each metacarpal phalangeal (MP) and interphalangeal (IP) joint in contact with each neurovascular digital pedicle and 3 ml was applied to each side of the metacarpal trapezius joint, together with 10 ml distributed subcutaneously throughout the palm of the hand and 10 ml evenly distributed on the back of the hand	Drug: ADSVF application in the right hand; 40 ml of fat was mixed with 2 ml of ADSVF and placed in 1-ml and 3-ml syringes. Using a 19-gauge blunt cannula (0.8 mm), 0.5 ml was applied to the radial and ulnar edge of each metacarpal phalangeal (MP) and interphalangeal (IP) joint in contact with each neurovascular digital pedicle and 3 ml was applied to each side of the metacarpal trapezius joint, together with 10 ml distributed subcutaneously throughout the palm of the hand and 10 ml evenly distributed on the back of the hand; Other Names: Medical treatment
NO_INTERVENTION: Control; Evolution and medical therapy effects were observed in the control group.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain before the treatment and every day during one week after the treatment, and each 28 days after de first week until the 168 day	Evaluation with Numerical Pain Rating Scale(NPRS) before, and after the intervention. The minimum value is 0 and maximum is 10. High value is worst	168 days
Frequency of Raynaud Phenomenon	Frequency, number of events per day/week;	168 days
Duration of Raynaud Phenomenon	Duration of minutes in every event.	168 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Digital Total active Motion	Goniometry, kapandjy Test	168 days
Digital oximetry	Transcutaneous Oximetry	168 days
Digital Ulcers	Number of ulcers	168 days
Health status and disability index	Evaluated by Sclerosis Health assessment Questionnarie (SHAQ) scale, before and at the end of the study. The value are from 0 to 3. A result >1.25 is worst	168 days
Hand Function	Cochin Scale, the values are from 0 to 90, higher values means poor function	168 days
Health-related quality of life, before de treatment and at the end of the study	Short Form 36 (SF-36) scale. High values is poor patient health	168 days
Vascularity of the nail bed	Videocapillaroscopy by field	168 days
Skin affection of the hand	Modified Rodnan scale, the values are from 0 to 51. High values higher skin fibrosis	168 days

Collaborators and Investigators

• Sponsor: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
• Collaborators: National Council of Science and Technology, Mexico
• Investigators: Study Chair: Carlos Hinojosa, MD, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 13, 2015
• Primary Completion (ACTUAL): May 1, 2019
• Study Completion (ACTUAL): May 1, 2020

Study Registration Dates

• First Submitted: May 10, 2020
• First Submitted That Met QC Criteria: May 10, 2020
• First Posted (ACTUAL): May 14, 2020

Study Record Updates

• Last Update Posted (ACTUAL): May 15, 2020
• Last Update Submitted That Met QC Criteria: May 13, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: Hand deformities in Systemic sclerosis
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Connective Tissue Diseases; Sclerosis; Scleroderma, Systemic; Scleroderma, Diffuse
• Other Study ID Numbers: SCI-1505-15/15-1; 290250 (OTHER_GRANT: CONACYT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No