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

• ClinicalTrials.gov Identifier: NCT04387825
• Recruitment Status: Completed
• First Posted: May 14, 2020
• Last Update Posted: May 15, 2020
• Sponsor: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
• Collaborator: National Council of Science and Technology, Mexico
• Information provided by (Responsible Party): Martín Iglesias, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Tracking Information

• First Submitted Date: May 10, 2020
• First Posted Date: May 14, 2020
• Last Update Posted Date: May 15, 2020
• Actual Study Start Date: August 13, 2015
• Actual Primary Completion Date: May 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 13, 2020)

• 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 [ Time Frame: 168 days ]
  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
• Frequency of Raynaud Phenomenon [ Time Frame: 168 days ]
  Frequency, number of events per day/week;
• Duration of Raynaud Phenomenon [ Time Frame: 168 days ]
  Duration of minutes in every event.

Original Primary Outcome Measures (submitted: May 10, 2020)

• 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 [ Time Frame: 168 days ]
  Evaluation with numerical pain rating scale before, and after the intervention
• Frequency of Raynaud Phenomenon [ Time Frame: 168 days ]
  Frequency, number of events per day/week;
• Duration of Raynaud Phenomenon [ Time Frame: 168 days ]
  Duration of minutes in every event.

Current Secondary Outcome Measures (submitted: May 13, 2020)

• Digital Total active Motion [ Time Frame: 168 days ]
  Goniometry, kapandjy Test
• Digital oximetry [ Time Frame: 168 days ]
  Transcutaneous Oximetry
• Digital Ulcers [ Time Frame: 168 days ]
  Number of ulcers
• Health status and disability index [ Time Frame: 168 days ]
  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
• Hand Function [ Time Frame: 168 days ]
  Cochin Scale, the values are from 0 to 90, higher values means poor function
• Health-related quality of life, before de treatment and at the end of the study [ Time Frame: 168 days ]
  Short Form 36 (SF-36) scale. High values is poor patient health
• Vascularity of the nail bed [ Time Frame: 168 days ]
  Videocapillaroscopy by field
• Skin affection of the hand [ Time Frame: 168 days ]
  Modified Rodnan scale, the values are from 0 to 51. High values higher skin fibrosis

Original Secondary Outcome Measures (submitted: May 10, 2020)

• Digital Total active Motion [ Time Frame: 168 days ]
  Goniometry, kapandjy Test
• Digital oximetry [ Time Frame: 168 days ]
  Transcutaneous Oximetry
• Digital Ulcers [ Time Frame: 168 days ]
  Number of ulcers
• Health status and disability index [ Time Frame: 168 days ]
  SHAQ scale
• Hand Function [ Time Frame: 168 days ]
  Cochin Scale
• Quality of Life before de treatment and at the end of the study [ Time Frame: 168 days ]
  SF-36 scale
• Vascularity of the nail bed [ Time Frame: 168 days ]
  Videocapillaroscopy by field
• Skin affection of the hand [ Time Frame: 168 days ]
  Modified Rodnan scale

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety Of Fat Micrografts With Adipose-Derived Stromal Vascular Fraction In Hands Of Patients With Systemic Sclerosis
• Official Title: 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

Brief Summary

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.

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
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Adipose Derived Stromal Vascular Fraction (ADSVF) was obtained in a laboratory by enzymatic digestion of fat graft harvested by liposuction. This ADSVF and micro fat grafts were applied into the hands with fibrosis and digital ulcers caused by Systemic Sclerosis in the experimental group. The control group was treated with medical treatment only

Masking: None (Open Label)
Primary Purpose: Treatment

• Condition: Systemic Sclerosis

Intervention

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 Name: Medical treatment

Study Arms

• 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
  Intervention: Drug: ADSVF application in the right hand
• No Intervention: Control
  Evolution and medical therapy effects were observed in the control group.

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 10, 2020): 20
• Original Actual Enrollment: Same as current
• Actual Study Completion Date: May 2020
• Actual Primary Completion Date: May 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Mexico

Administrative Information

• NCT Number: NCT04387825
• Other Study ID Numbers: SCI-1505-15/15-1; 290250 ( Other Grant/Funding Number: CONACYT )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Martín Iglesias, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
• Original Responsible Party: Same as current
• Current Study Sponsor: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
• Original Study Sponsor: Same as current
• Collaborators: National Council of Science and Technology, Mexico

Investigators

• Study Chair: Carlos Hinojosa, MD; Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

• PRS Account: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
• Verification Date: May 2020