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Safety and Efficacy of Adipose Derived Stem Cells in Refractory Rheumatoid Arthritis, Systemic Lupus Erythematosus or Sharp's Syndrome

Phase 1
Terminated
Conditions
Sharp's Syndrome
Rheumatoid Arthritis
Systemic Lupus Erythematosus
Interventions
Other: Intravenous injection of Stromal Vascular Fraction Cells (SVF) containing ADSCs
Other: Lipoaspiration
Registration Number
NCT02741362
Lead Sponsor
Arkansas Heart Hospital
Brief Summary

This is a Phase I-II open- label single-dose study in subjects with significant refractory Rheumatoid Arthritis (RA), relapsing Systemic Lupus Erythematosus (SLE) or Sharp's Syndrome (SS).

This study will enroll a minimum of 20 subjects for RA, 20 subjects for SLE and 20 patients for SS. 6 week data of serum Tumor Necrosis Factor- alpha (TNFa), Interleukin- 6 (IL-6), C- Reactive Protein (CRP), Erythrocyte Sedimentation Rate (ESR), Cluster of Differentiation (CD)4 +CD25 + Forkhead box P3(Foxp3) + regulatory T cells, Disease Activity Score for 28 joints (DAS-28) score and pain score will be collected in all patients who are enrolled in the study for the RA group (Baseline and 6 weeks after). For the SLE group, Transforming Growth Factor- beta (TGF-β), TNFa, IL-6, Interleukin- 17 (IL-17), CD3+CD8-IL17A+ T helper-17 (Th17) cells, CD4+CD25+Foxp3+ regulatory T cells and the Systemic Lupus Erythematosus Quality of Life Questionnaire (SLEQoL) score will be collected in all the subjects of this group. SS group will undergo the assessments of RA and SLE. Prior to the stem cell treatment, the patient will be assessed for 6 weeks by all the previously mentioned markers. Then, patients will receive the infusion of stromal vascular fraction cells containing the adult adipose derived stem cells 'aADSC' (single intravenous dose). The disease- modifying anti-rheumatic drugs (DMARDs) or the standard SLE treatment will not be interrupted with the exception of systemic steroids (excluding minimal maintenance dose of one steroid) during the duration of the study. Follow up visits will take place at 6 weeks, 3 Months and 6 Months after the cell infusion. Safety will be monitored on an ongoing basis, and an interim safety review will be conducted by the Investigator(s) and Sponsor after the first 10 patients have been enrolled and treated in each group.

Detailed Description

Not available

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
2
Inclusion Criteria
  1. Males and Females ≥18 years
  2. Cognitive competitiveness.
  3. Diagnosis of refractory RA (patient's poor response of 3 months of DMARDs determined and documented by a rheumatologist) ,diagnosis of relapsing SLE (more than 2 episodes in a year during optimal medical SLE therapy) or diagnosis of Sharp syndrome (Alarcon-Segovia's criteria: patients with U1 Ribonucleic protein (RNP) ≥ 1:1600, and three of the following: Swollen hands, Synovitis, Myositis, Raynauld's phenomenon, Acrosclerosis)
  4. Life expectancy greater than 8 months
  5. Ability to understand and provide signed informed consent, or have a designated legal guardian or spouse legally able and willing to make such decisions on the subject's behalf
  6. Reasonable expectation that patient will receive standard post-treatment care and attend all scheduled safety follow-up visits
  7. No changes in active pulmonary medications for heart failure during the two weeks prior enrollment.
  8. Written informed consent
Exclusion Criteria
  1. Currently on systemic steroids (if chronic steroid therapy cannot be stopped, the patient will qualify if he/she is on a minimum maintenance dose per SLE, RA or SS guidelines of only one systemic steroid and constituting a bioequivalent to normal endogenous levels of that hormone).
  2. Dementia.
  3. Presence of immune deficiency.
  4. Currently on NSAIDs, TNFa inhibitors, Calcium channel blockers or P2Y12 inhibitors
  5. Complicated type 2 diabetes mellitus (presence of diabetic foot, advanced kidney disease or retinopathy).
  6. History of cancer within the past 5 years.
  7. Presence of any other clinically-significant medical condition, psychiatric condition, or laboratory abnormality, that in the judgment of the Investigator or Sponsor for which participation in the study would pose a safety risk to the subject
  8. Participation in another study with an investigational drug or device within 3 weeks prior to treatment
  9. History within the past year of drug or alcohol abuse.
  10. Females known to be pregnant, lactating or having a positive pregnancy test (will be tested during screening) or planning to become pregnant during the study.
  11. Inability to comply with the conditions of the protocol.
  12. Porphyria.
  13. Allergy to sodium citrate or any "caine" type of local anesthetic.
  14. Patient scheduled for hospice care.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
ADSC armLipoaspirationSingle intravenous administration of Stromal Vacsular Fraction (SVF) cells soinating Adipose Derived Stem Cells (ADSC) 6 week baseline data prior to the injection of ADSC will be collected. 6 week, 3 months and 6 months follow up data will be compared against baseline.
ADSC armIntravenous injection of Stromal Vascular Fraction Cells (SVF) containing ADSCsSingle intravenous administration of Stromal Vacsular Fraction (SVF) cells soinating Adipose Derived Stem Cells (ADSC) 6 week baseline data prior to the injection of ADSC will be collected. 6 week, 3 months and 6 months follow up data will be compared against baseline.
Primary Outcome Measures
NameTimeMethod
Frequency of Adverse Events (AE) and Serious Adverse Events (SAE) during a 6 month follow up period.6 Months
Secondary Outcome Measures
NameTimeMethod
Quality of Life Questionnaires for SLE/ RA6 Months

SLEQoL score

Serum C- reactive protein (CRP)6 Months

C- reactive protein (CRP)

Quality of Life Questionnaires for RA6 Months

DAS-28 score

Erythrocyte Sedimentation Rate (ESR)6 Months

Erythrocyte Sedimentation Rate (ESR)

Serum Transforming Growth Factor- beta (TGFb)6 Months

Transforming Growth Factor- beta (TGFb)

Serum Interleukin- 6 (IL-6)6 Months

Interleukin- 6 (IL-6)

Blood Flow Cytometry for CD4+CD25+Foxp3+ regulatory T cells6 Months

CD4+CD25+Foxp3+ regulatory T cells,

Blood Flow Cytometry for CD3+CD8-IL17A+TH17 cells6 Months

CD3+CD8-IL17A+TH17 cells

Serum Interleukin- 17 (IL-17)6 Months

Interleukin- 17 (IL-17)

Serum Tumor Necrosis Factor- alpha (TNFa)6 Months

Tumor Necrosis Factor- alpha (TNFa)

Trial Locations

Locations (1)

Arkansas Heart Hospital

🇺🇸

Little Rock, Arkansas, United States

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