Injection of Autologous Adipose-derived Stromal Vascular Fraction in the Finger of Systemic Sclerosis Patients

Safety, Tolerability and Potential Efficacy of Injection of Autologous Adipose-derived Stromal Vascular Fraction in the Finger of Systemic Sclerosis Patients

Status

Completed

Phases

Early Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03060551

Enrollment

Registered

2017-02-23

Start date

2018-07-01

Completion date

2019-12-30

Last updated

2020-10-08

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Systemic Sclerosis

Keywords

stromal vascular fraction, hand disability, mesenchymal stem cells, phase I trial

Brief summary

This study outlines the safety of the autologous SVF cells injection in the hands of patients with SSc. Preliminary assessments at 6 months will suggest potential efficacy needing confirmation in a randomised placebo-controlled trial on a larger population

Detailed description

In patients with systemic sclerosis(scleroderma, SSc), impaired hand function greatly contributes to disability and reduced quality of life, and is insufficiently relived by currently available therapies. Adipose tissue-derived stromal vascular fraction (SVF) is increasingly recognized as an easily accessible source of regenerative cells with therapeutic potential in ischaemic or autoimmune disease. The investigators aimed to measure for the first time the safety, tolerability, and potential efficacy of autologous SVF cells local injections in patients with SSc with hand disability.

Interventions

PROCEDURESVF injection

SVF is increasingly recognised as an easily accessible source of regenerative cells with therapeutic potential in ischaemic or autoimmune disease. We aimed to measure for the first time the safety, tolerability and potential efficacy of autologous SVF cells local injections in patients with systemic sclerosis

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Intervention model description

Systemic sclerosis patients with hand disability, planning 24 weeks of follow-up period Autologous adipose tissue-derived stromal vascular fraction(SVF) injected into the subcutaneous tissue of each finger in contact with neurovascular pedicles.

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* age over 18 year old * Cochin Hand Function Scale (CHFS) \> 20/90

Exclusion criteria

* new vasodilators or immunosuppressive therapy for SSc in the 3 months prior to enrolment * new vasodilators or immunosuppressive therapy for SSc during the 6-month follow-up * clinical or radiological signs of digital infection * positive status for HIV * positive status for hepatitis B or C * positive status for human T-cell leukemia virus 1-2 * positive status for syphilis * pregnancy * BMI less than 17kg/m2

Design outcomes

Primary

Measure	Time frame	Description
Raynaud's Condition Scale	Baseline, 2 weeks, 6 weeks, 12 weeks, 24 weeks	The severity of Raynaud's phenomenon was assessed using the Raynaud's condition scale (ranging 0 to 10, with higher scores representing more severe Raynaud's phenomenon)
Hand Visual Analogue Scale	Baseline, 2 weeks, 6 weeks, 12 weeks, 24 weeks	Hand pain was assessed using the Hand visual analogue scale (ranging 0 to 10, with higher scores representing more severe pain)
Colchin Hand Function Scale	Baseline, 2 weeks, 6 weeks, 12 weeks, 24 weeks	The Colchin hand function scale (CHFS, ranging 0 to 90, with higher scores representing more deteriorated hand function) scores
Kapandji Score (Ranging 0 to 10) - Dominant Hand	Baseline, 2 weeks, 6 weeks, 12 weeks, 24 weeks	Kapandji score (ranging 0 to 10) is validated measures in past studies as outcomes for hand disability. The Kapandji score is a tool useful for assessing the opposition of the thumb, based on where on their hand the patient is able to touch with the tip of their thumb. A score of 0 indicates no opposition, a score of 10 indicates maximal opposition.
Kapandji Score (Non-dominant Hand)	Baseline, 2 weeks, 6 weeks, 12 weeks, 24 weeks	Kapandji score (ranging 0 to 10) is validated measures in past studies as outcomes for hand disability. The Kapandji score is a tool useful for assessing the opposition of the thumb, based on where on their hand the patient is able to touch with the tip of their thumb. A score of 0 indicates no opposition, a score of 10 indicates maximal opposition.
Disease-related QOL (Quality of Life) : EuroQol-5 Dimensions Time Trade-off (EQ-5D TTO)	Baseline, 2 weeks, 6 weeks, 12 weeks, 24 weeks	Disease-related QOL (quality of life) was measured by EuroQol-5 dimensions time trade-off (EQ-5D TTO, ranging 0 to 1, with higher values representing better QOL) values
Disease-related QOL (Quality of Life) : EuroQol Visual Analog Scale (EQ VAS)	Baseline, 2 weeks, 6 weeks, 12 weeks, 24 weeks	Disease-related QOL (quality of life) : EuroQol visual analog scale (EQ VAS, ranging 0 to 100, with higher scores representing better QOL)
Disease-related QOL (Quality of Life) : Health Assessment Questionnaire (HAQ)	Baseline, 2 weeks, 6 weeks, 12 weeks, 24 weeks	Disease-related QOL (quality of life) : health assessment questionnaire (HAQ, ranging 0 to 3, with higher scores meaning lower QOL)
The Degree of Hand Edema (Right)	Baseline, 2 weeks, 6 weeks, 12 weeks, 24 weeks	The finger circumferences of the second to the fifth fingers measured in the middle portion of each proximal phalanx were used to assess the degree of hand edema
The Degree of Hand Edema (Left)	Baseline, 2 weeks, 6 weeks, 12 weeks, 24 weeks	The finger circumferences of the second to the fifth fingers measured in the middle portion of each proximal phalanx were used to assess the degree of hand edema

Secondary

Measure	Time frame	Description
Changes of Nailfold Capillary Microscopic Findings (Irregularly Enlarged Capillaries)	Baseline, 2 weeks, 6 weeks, 12 weeks, 24 weeks	In order to assess the severity of microangiopathies in both fingers, a semiquantitative scoring system for nailfold capillary microscopic findings was adopted. A total of six parameters (irregularly enlarged capillaries, giant capillaries, hemorrhages, loss of capillaries, disorganization of the vascular array and capillary ramifications) were measured using the semiquantitative manner on the scale ranging 0 to 3, indicating more severe as scores were higher. Each parameter was scored for four fingers of both hands, except thumbs, and the median score value of each parameter in both hands was finally presented.
Changes of Nailfold Capillary Microscopic Findings (Giant Capillaries)	Baseline, 2 weeks, 6 weeks, 12 weeks, 24 weeks	In order to assess the severity of microangiopathies in both fingers, a semiquantitative scoring system for nailfold capillary microscopic findings was adopted. A total of six parameters (irregularly enlarged capillaries, giant capillaries, hemorrhages, loss of capillaries, disorganization of the vascular array and capillary ramifications) were measured using the semiquantitative manner on the scale ranging 0 to 3, indicating more severe as scores were higher. Each parameter was scored for four fingers of both hands, except thumbs, and the median score value of each parameter in both hands was finally presented.
Changes of Nailfold Capillary Microscopic Findings (Hemorrhages)	Baseline, 2 weeks, 6 weeks, 12 weeks, 24 weeks	In order to assess the severity of microangiopathies in both fingers, a semiquantitative scoring system for nailfold capillary microscopic findings was adopted. A total of six parameters (irregularly enlarged capillaries, giant capillaries, hemorrhages, loss of capillaries, disorganization of the vascular array and capillary ramifications) were measured using the semiquantitative manner on the scale ranging 0 to 3, indicating more severe as scores were higher. Each parameter was scored for four fingers of both hands, except thumbs, and the median score value of each parameter in both hands was finally presented.
Changes of Nailfold Capillary Microscopic Findings (Loss of Capillaries)	Baseline, 2 weeks, 6 weeks, 12 weeks, 24 weeks	In order to assess the severity of microangiopathies in both fingers, a semiquantitative scoring system for nailfold capillary microscopic findings was adopted. A total of six parameters (irregularly enlarged capillaries, giant capillaries, hemorrhages, loss of capillaries, disorganization of the vascular array and capillary ramifications) were measured using the semiquantitative manner on the scale ranging 0 to 3, indicating more severe as scores were higher. Each parameter was scored for four fingers of both hands, except thumbs, and the median score value of each parameter in both hands was finally presented.
Changes of Nailfold Capillary Microscopic Findings (Disorganization of the Vascular Array)	Baseline, 2 weeks, 6 weeks, 12 weeks, 24 weeks	In order to assess the severity of microangiopathies in both fingers, a semiquantitative scoring system for nailfold capillary microscopic findings was adopted. A total of six parameters (irregularly enlarged capillaries, giant capillaries, hemorrhages, loss of capillaries, disorganization of the vascular array and capillary ramifications) were measured using the semiquantitative manner on the scale ranging 0 to 3, indicating more severe as scores were higher. Each parameter was scored for four fingers of both hands, except thumbs, and the median score value of each parameter in both hands was finally presented.
Changes of Nailfold Capillary Microscopic Findings (Capillary Ramifications)	Baseline, 2 weeks, 6 weeks, 12 weeks, 24 weeks	In order to assess the severity of microangiopathies in both fingers, a semiquantitative scoring system for nailfold capillary microscopic findings was adopted. A total of six parameters (irregularly enlarged capillaries, giant capillaries, hemorrhages, loss of capillaries, disorganization of the vascular array and capillary ramifications) were measured using the semiquantitative manner on the scale ranging 0 to 3, indicating more severe as scores were higher. Each parameter was scored for four fingers of both hands, except thumbs, and the median score value of each parameter in both hands was finally presented.

Countries

South Korea

Participant flow

Recruitment details

Between July 2018 and December 2019, a total of twenty subjects were enrolled in this single center, open label, phase I trial.

Pre-assignment details

Among the initially enrolled patients, one patient refused further procedures after baseline evaluation, while another patient dropped out due to complications during local anesthesia right before SVF injection.

Participants by arm

Arm	Count
SVF Injection SVF was obtained from lipoaspirates, using an automated processing system, and subsequently injected into the subcutaneous tissue of each finger in contact with neurovascular pedicles SVF injection: SVF is increasingly recognised as an easily accessible source of regenerative cells with therapeutic potential in ischaemic or autoimmune disease. We aimed to measure for the first time the safety, tolerability and potential efficacy of autologous SVF cells local injections in patients with systemic sclerosis	20
Total	20

Arm

Count

SVF Injection

SVF was obtained from lipoaspirates, using an automated processing system, and subsequently injected into the subcutaneous tissue of each finger in contact with neurovascular pedicles SVF injection: SVF is increasingly recognised as an easily accessible source of regenerative cells with therapeutic potential in ischaemic or autoimmune disease. We aimed to measure for the first time the safety, tolerability and potential efficacy of autologous SVF cells local injections in patients with systemic sclerosis

Total

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Adverse Event	1
Overall Study	Withdrawal by Subject	1

Baseline characteristics

Characteristic	SVF Injection	—
Age, Continuous	47 years	—
Anti-centromere antibody	4 Participants	—
Anti-nuclear antibody	18 Participants	—
Anti-Ro/SSA antibody	4 Participants	—
Anti-Scl70 antibody	13 Participants	—
Anti-U1 RNP antibody	5 Participants	—
Body mass index (BMI) kg/m2	21.5 kg/m2	—
Diabetes mellitus	0 Participants	—
Disease duration (years)	6 years	—
Hand dominance (right)	18 Participants	—
History of renal crisis	1 Participants	—
Hypertension	0 Participants	—
Interstitial lung disease	10 Participants	—
Medication status (Aloprostadil)	3 Participants	—
Medication status (Azathioprine)	5 Participants	—
Medication status (calcium channel blocker)	9 Participants	—
Medication status (Endothelial receptor antagonist))	1 Participants	—
Medication status (Glucocorticoid)	13 Participants	—
Medication status (Methotrexate)	8 Participants	—
Medication status (prostacyclin)	2 Participants	—
Osteoporosis	6 Participants	—
Pulmonary hypertension	1 Participants	—
Race and Ethnicity Not Collected	—	— Participants
Region of Enrollment South Korea	20 participants	—
Reynaud's phenomenon duration	9 years	—
Sex: Female, Male Female	15 Participants	—
Sex: Female, Male Male	3 Participants	—
Smoking history (Current or ex-)	3 Participants	—
Types of cutaneous manisfetations (diffuse or limited) Diffuse	8 Participants	—
Types of cutaneous manisfetations (diffuse or limited) Limited	10 Participants	—

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 20
other Total, other adverse events	5 / 20
serious Total, serious adverse events	0 / 20

Outcome results

Primary

Colchin Hand Function Scale

The Colchin hand function scale (CHFS, ranging 0 to 90, with higher scores representing more deteriorated hand function) scores