Safety, Tolerability and Preliminary Efficacy of Adipose Derive Stem Cells for Patients With COPD

A Phase I Open- Label Study to Assess the Safety, Tolerability, and Preliminary Efficacy of a Single Intravenous Dose of Autologous Adipose Stem Cell (Adult Human) to Subjects With Chronic Obstructive Pulmonary Disease

The purpose of this study is: 1.- to assess the safety and tolerability of autologous adipose derived stem cells (aADSC) administered intravenously in patients with chronic obstructive pulmonary disease, and 2.- to assess if this therapy results in less decrease of lung function parameters (FEV1, FEV1/FVC and 6 min walking distance) compared with a control baseline of 6 weeks.

Patients will be followed up for 12 months after the therapy.

Study Overview

• Status: Terminated
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Biological: ADSCs administration

Detailed Description

STUDY DESIGN This is a Phase I open- label single-dose study in subjects with significant COPD. This is an expanded safety cohort. The investigators will enroll a minimum of 30 subjects. 6 week data of FEV1, FEV1/FVC, DLCO and 6 min walking distance values will be collected in all patients who are enrolled in the study (Baseline and 6 weeks after). Prior to the stem cell treatment, the patient will be assessed for 6 weeks by pulmonary function tests and 6 min walk tests. Then, patients will receive the infusion of stromal vascular fraction cells containing the aADSC (single intravenous dose). The standard therapy of COPD patients will not be interrupted during the duration of the study. 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 20 patients have been enrolled and treated.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • Arkansas Heart Hospital
    • Little Rock, Arkansas, United States, 72211
      • Arkansas Site Management Services LLC

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:

1. Males and Females ≥18 years.
2. Cognitive competitiveness.
3. Diagnosis of at least moderate COPD (postbronchodilator FEV1/FVC < 70% (<0.7), FEV1 < 80% predicted).
4. Diffusing capacity impairment (DLCO) assessed by single breath test (corrected for alveolar volume, 'DLVA').
5. Life expectancy greater than 12 months.
6. 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.
7. Reasonable expectation that patient will receive standard post-treatment care and attend all scheduled safety follow-up visits.
8. No changes in active pulmonary medications for heart failure during the two weeks prior enrollment.

10. Written informed consent. 11. Non-smoker or Past smoker, with 20 pack-years or more history

Exclusion Criteria:

1. Current smokers.
2. Unstable coronary disease.
3. Patients with industrial exposure to silica and/or asbestos or giant bullae.
4. Uncontrolled seizure disorder.
5. Dementia.
6. Presence of immune deficiency or autoimmune disease.
7. Alpha- 1 antitrypsin deficiency.
8. Cor pulmonale or diastolic heart failure NYHA class III or IV
9. Type 1 diabetes mellitus
10. Complicated type 2 diabetes mellitus.
11. Active tuberculosis or severe lung damage due to tuberculosis (extensive cavitation).
12. History of cancer within the past 5 years.
13. Clinically-significant hematologic, hepatic, or renal impairment as determined by screening clinical laboratory tests.
14. Systemic corticosteroids, cytostatics, immunosuppressive drug therapy (cyclophosphamide, methotrexate, cyclosporine, azathioprine, etc.), and DNA depleting or cytotoxic drugs taken within four weeks prior to study treatment.
15. Porphyria.
16. Allergy to sodium citrate or any "caine" type of local anesthetic.
17. Abnormal findings could include: known HIV infection or other immunodeficiency state, chronic active viral infection (such as hepatitis B or C), acute systemic infections (defined as patients undergoing treatment with antibiotics), gastrointestinal tract bleeding, or any severe or acute concomitant illness or injury.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ADSCs administration; Patients with Chronic Obstructive Pulmonary Disease will be treated with a single dose of autologous adipose derived stem cells. Stem cells will be isolated using standard Lipoaspiration procedure under sterile conditions.	Biological: ADSCs administration; 100- 240 cc of lipoaspirate will be extracted from the patient. The stromal vascular fraction (SVF) will be isolated with minimal manipulation. The cell pellet will be reconstituted in saline solution and administered intravenously to the patient.; Other Names: Autologous Adipose Derived Stem Cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of adipose derived stem cells (ADSC) in Patient with COPD	Safety/tolerability of Adipose Derived Stem Cell (ADSC) in patients with Chronic Obstructive Pulmonary Disease (COPD) during the twelve-month study period as determined by the incidence and severity of of adverse events.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of ADSC in improving Shortness of Breath (SOB)	The change (decrease) in patient Shortness Of Breath (SOB) as compared to baseline, measured in breath per minute, after administration of adipose derived stem cells (ADSC)	2, 6 and 12 months
Efficacy of ADSC In Pulmonary Function Test (PFTs)	The change (improvement) in Pulmonary Function Test (PFTs) after administration of adipose derived stem cells (ADSC) as compared to baseline.	2, 6, 12 months
Efficacy of adipose derived stem cell in 6 MWT	Improvement in patient ability to walk as measure using a 6 minute walk test ( in meter) as compared to baseline	2, 6, 12 months
Efficacy of adipose derived stem cells in patient's perceived exertion.	The change from baseline in patient perceived exertion as measure using the modified BORG scale or Rate of perceive exertion (RPE) which ranges from 1(no perceived exertion at all) to 10 (maximum perceived exertion)	2, 6, 12 months
Efficacy in Quality of life using George's Respiratory Questionnaire	The change from baseline in patient quality of life as measure using the George's Respiratory Questionnaire	2, 6, 12 months
Efficacy in Quality of life using the Chronic Respiratory questionnaires	The change from baseline in patient quality of life as measure using the Chronic Respiratory Questionnaire	2, 6, 12 months

Collaborators and Investigators

• Sponsor: Arkansas Heart Hospital
• Investigators: Principal Investigator: Jason Holder, MD, Arkansas Heart Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2013
• Primary Completion (Actual): October 29, 2018
• Study Completion (Actual): October 29, 2018

Study Registration Dates

• First Submitted: May 21, 2014
• First Submitted That Met QC Criteria: June 11, 2014
• First Posted (Estimate): June 12, 2014

Study Record Updates

• Last Update Posted (Actual): January 27, 2020
• Last Update Submitted That Met QC Criteria: January 23, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: Chronic Obstructive Pulmonary Disease; Pulmonary Function Tests; Adipose derived stem cells; Stromal vascular fraction cells
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: ICMS-2013-25