Clinical trial NCT05669261: Treatment of Long COVID Symptoms Utilizing Autologous Stem Cells Following COVID-19 Infection
Official title: A PILOT STUDY ON RESEARCH TREATMENT OF LONG COVID POST-ACUTE SEQUELAE OF SARS CoV-2 INFECTION ("PASC") USING ATCell™
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Long COVID
Keywords: Long COVID
Post Acute Sequelae
Lead sponsor: American CryoStem Corporation
Sponsor class: INDUSTRY
First posted: 2022-12-30
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: The proposed study is a randomized single-center, double-blinded, placebo controlled standard of care plus study. Once safety has been certified by IRB/ HRPP, the study will be unblinded and participants that received the placebo treatment will be offered the opportunity to crossover and receive 150 million cell ATCell™ autologous treatment with the same monitoring and clinical support afforded to the first treatment cohort
Primary purpose: TREATMENT

Brief summary: The project is described as a Phase 1 Clinical Safety Study intended to provide preliminary assessments of the safety, tolerability, and secondarily to be vigilant for signals of amelioration of symptoms associated with Post-Acute Sequelae of SARS-CoV-2 infection

Detailed description: The proposed study is a randomized single-center, double-blinded, placebo controlled standard of care plus study. Each participant will continue to receive standard of care treatment for their current diagnosis and be afforded the opportunity to add any additional care as needed that may include care for behavioral health concerns. In the proposed study, safety of a single administration of expanded autologous lines at a total dose exposure of 150 million cells ("ATCell™") will be assessed. Each ATCell™ cell batch will be derived from ex vivo expanded stromal vascular fraction (SVF) of a participant's own adipose tissue. SVF is collected by liposuction and expanded. Briefly, ATCell suspended in Lactated Ringer's with 5% dextrose solution, or a placebo of Lactated Ringers 5% dextrose solution will be administered once to each participant. Safety will be evaluated through clinical assessments and laboratory test results comparing treatment cohort participant's baseline assessments and laboratory test results. Following completion of follow up period as defined in the schedule of events, the study will be unblinded, the results reviewed by the Institutional Review Board (IRB) and Human Research Protection Program (HRPP). Once safety has been reviewed by IRB/ HRPP, the study will be unblinded and participants that received the placebo treatment will be offered the opportunity to crossover and receive 150 million cell ATCell™ autologous treatment with the same monitoring and clinical support afforded to the first treatment cohort.

Eligibility criteria: Inclusion Criteria:

1. Active duty service members: military retirees, DEERS eligible dependents who are Tricare beneficiaries only (Department of Defense (DoD) investigational sites only)
2. Participants ages of 18 years and above
3. Documentation of a positive COVID-19 polymerase chain reaction (PCR) test or strong history of SARS-CoV-2 exposure with positive supportive serology
4. Male or female or other gender
5. Individuals with established diagnosis of PASC
6. Subjects with moderate to severe levels of PASC based on synthesis of multiple assessment modalities provided by the multispecialty study team.
7. PASC phenotype to include signs and symptoms of fatigue and low endurance and either Autonomic Disorder or Dyspnea or both.
8. Subjects who are able to comprehend the consent procedure and follow the treatment process.
9. Female participants of childbearing potential and at risk of pregnancy during the study must agree to use 2 highly effective methods of contraception throughout the study and for 112 days after the last study visit.
10. Female participant who are not of childbearing potential (i.e,. must meet at least one (1) of the following criteria): have undergone a hysterectomy and/or bilateral oophorectomy, or ovarian failure .
11. For male subjects who can father a child and are having intercourse with females of childbearing potential who are not using adequate contraception, willingness to use a barrier method of contraception (condom) from the start of study therapy until ≥ 90 days after the end of the study and to refrain from sperm donation until ≥ 90 days after the end of the study.
12. Achieved postmenopausal status defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or psychological cause and have a serum follicle stimulating hormone (FSH) level confirming the post-menopausal state.
13. Individuals who are willing and able to comply with lifestyle guidelines, scheduled visits, treatment plan, laboratory tests, and other study procedures through the end of the final study visit.
14. Individuals with the following Vital Signs:

    1. Systolic Blood Pressure of \> 100 or \< 140 (mmHg)
    2. Diastolic Blood Pressure of \> 60 or \<90 (mmHg)
    3. Heart Rate of \> 60 or \< 100 (bpm) (beats per minute)
    4. Temperature of \< 38°C (afebrile)
    5. Respiratory Rate of \> 12 or \< 20 (bpm) (breaths per minute)
    6. Pulse Ox greater than \>95% on room air
    7. BMI \< 28

Exclusion Criteria:

5.3.7.4 Exclusion Criteria:

1. Subjects with documented past or current history of severe depression, suicidal ideations or suicidal attempts.
2. Subjects who are unable to comprehend the content of informed consent
3. Female subjects who are pregnant or who are not willing to practice effective contraception during and for 112 days following the last study visit
4. Female subjects who are breastfeeding
5. History of abnormal brain or spinal MRI for presence of thromboembolic events.
6. Recent traumatic brain injury or other concussive event within 12 months of medical history review
7. History of abnormal Echocardiogram for cardiac structure or function in the last 10 years.
8. Prior history of postural orthostatic tachycardia syndrome predating diagnosis of SARS-CoV2 infection
9. Uncontrolled hypertension or hyperlipidemia
10. Prior to COVID diagnosis, the presence of abnormal chest x-ray for any parenchymal disease, or,

    1. Active tuberculosis or ongoing treatment for tuberculosis or any acute or chronic infection affecting lung
    2. Chronic lung disease due to fibrosis or autoimmune inflammation such as sarcoidosis or rheumatoid arthritis, vasculitis or lupus
    3. Lung cancer
    4. Asthma
    5. Chronic obstructive pulmonary disease (COPD)
    6. Emphysema
    7. Disorders of upper airway, larynx, or trachea that pose potential complications in a state of emergency for airway management due to SAE.
    8. Disorders of pleura that affects pulmonary functions
11. Prior history of connective tissue diseases
12. History of severe hospitalization from COVID-19 or other respiratory infection requiring mechanical ventilation or extracorporeal membrane oxygenation (ECMO)
13. Pulse oxygenation readings \<95% on room air during screening exam
14. History of pulmonary embolism during lifetime
15. Prior history of deep venous thromboses, stroke or myocardial infarction
16. Any thrombophilia, including factor V Leiden, protein C deficiency, and protein S deficiency
17. Ongoing pharmaceutical or radiation treatment for infection or malignancy
18. Prior positive test for any of the following without demonstration of resolution: viral Hepatitis B or C (HBV, HCV), Human Immunodeficiency virus -1 or -2 (HIV1 or HIV2), Human T cell leukemia virus -I or -II (HTLV-1 or HTLV-II), West Nile, Zika, Syphilis.
19. Use of any immunosuppressive, immune modulating drugs include calcineurin inhibitors, antimetabolites, alkylating agents, for greater than 14 consecutive days over the last 3 months
20. Actively listing (or expected listing) for transplant of any organ, other than corneal, bone, skin, ligament or tendon transplant.
21. Be an organ transplant recipient in the past, other than for corneal, bone, skin, ligament or tendon transplant.
22. History of malignant tumor within the past 10 years for breast cancer and 5 years for all other cancers.
23. Individuals allergic to local anesthetics
24. Individuals with inadequate subcutaneous tissue to allow appropriate lipoaspirate (i.e., fat extraction)
25. Any history of autoimmune illnesses including but not limited to: Multiple sclerosis, Crohn's disease, Myasthenia gravis, Hashimoto's thyroiditis, psoriatic arthritis, Pernicious anemia/atrophic gastritis, Guillain-Barre, Chronic inflammatory demyelinating polyneuropathy, Type 1 diabetes mellitus, Inflammatory bowel disease, Systemic lupus erythematosus, vasculitis, Immune thrombocytopenic purpura, inflammatory muscle disease or Rheumatoid arthritis, Rheumatic fever.
26. Uncontrolled type 2 diabetes
27. Any abnormal test result, in the opinion of the PI and the study team, that may compromise the safety or compliance of the participant or preclude successful completion of the study, or that may compromise the validity of the study.
28. Individuals expecting retirement, military separation, deployment or relocation in the next 12 months.

Primary outcomes:
measure: Assessment of the Incidence of Serious Adverse Events (SAEs)
timeFrame: Upon completion of final post treatment clinical visit of all participants
measure: Assessment of change in Health Status using the 36 item Short Form Health Survey (SF-36)
timeFrame: One week post administration
measure: Assessment of change in Health Status using the 36 item Short Form Health Survey (SF-36)
timeFrame: Two weeks post administration
measure: Assessment of change in Health Status using the 36 item Short Form Health Survey (SF-36)
timeFrame: Three weeks post administration
measure: Assessment of change in Health Status using the 36 item Short Form Health Survey (SF-36)
timeFrame: Four weeks post administration
Secondary outcomes:
measure: Assessment of Changes in Exosome/Cytokine/Chemokine Testing
timeFrame: Once per week for four weeks post administration
measure: Assessment of change in completion time -Six-minute walk test (6MWT)
timeFrame: Four weeks post administration
measure: Assessment of Change in Complete blood count with differential (CBC with diff) Laboratory Testing Results
timeFrame: Each week for four weeks post administration
measure: Assessment of Change in Lactate dehydrogenase (LDH) Laboratory Testing Results
timeFrame: Each week for four weeks post administration
measure: Assessment of Change in Prothrombin time/partial thromboplastin time (PT/PTT Coagulation factors II) Laboratory Testing Results
timeFrame: Each week for four weeks post administration
measure: Assessment of Change in Troponin Laboratory Testing Results
timeFrame: Each week for four weeks post administration
measure: Assessment of Change in D-dimer Laboratory Testing Results
timeFrame: Each week for four weeks post administration
measure: Assessment of Change in Fibrinogen (Coagulation factors II) Laboratory Testing Results
timeFrame: Each week for four weeks post administration
measure: Assessment of Change in estimated glomerular filtration rate Laboratory Testing Results
timeFrame: Each week for four weeks post administration
measure: Assessment of Change in Urinalyses Laboratory Testing Results
timeFrame: Each week for four weeks post administration
measure: Assessment of Change in Spot creatinine Laboratory Testing Results
timeFrame: Each week for four weeks post administration
Other outcomes:
Locations:
Study officials:
affiliation: American CryoStem Corporation
name: Anthony Y Dudzinski
role: STUDY_DIRECTOR
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