Treatment of Long COVID Symptoms Utilizing Autologous Stem Cells Following COVID-19 Infection

NCT05669261 | Unknown Phase 1 DMC FDA Drug

• 1 other identifier: 0001_CRYO_LC19_ADSC_001
• Study Type: interventional
• Target: 20
• Locations: 0 countries
• Sites: N/A

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

Conditions

Long COVID

Keywords

Long COVID; Post Acute Sequelae

Outcome Measures

Primary Outcomes (5)

• Assessment of the Incidence of Serious Adverse Events (SAEs)

  Observed Adverse Events (AE's) in the placebo control group will be compared to observed AE in the experimental treatment, if any, in order to assess safety of the experimental treatment.

  Upon completion of final post treatment clinical visit of all participants

• Assessment of change in Health Status using the 36 item Short Form Health Survey (SF-36)

  Completed by Participant as a part of physician visits at baseline, and once per week following treatment. Scores of completed SF-36 will be numerically determined and compared to baseline. Changes against baseline will be represented numerically (positive or negative).The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability.

  One week post administration

• Assessment of change in Health Status using the 36 item Short Form Health Survey (SF-36)

  Completed by Participant as a part of physician visits at baseline, and once per week following treatment. Scores of completed SF-36 will be numerically determined and compared to baseline. Changes against baseline will be represented numerically (positive or negative).The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability.

  Two weeks post administration

• Assessment of change in Health Status using the 36 item Short Form Health Survey (SF-36)

  Completed by Participant as a part of physician visits at baseline, and once per week following treatment. Scores of completed SF-36 will be numerically determined and compared to baseline. Changes against baseline will be represented numerically (positive or negative).The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability.

  Three weeks post administration

• Assessment of change in Health Status using the 36 item Short Form Health Survey (SF-36)

  Completed by Participant as a part of physician visits at baseline, and once per week following treatment. Scores of completed SF-36 will be numerically determined and compared to baseline. Changes against baseline will be represented numerically (positive or negative).The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability.

  Four weeks post administration

Secondary Outcomes (11)

• Assessment of Changes in Exosome/Cytokine/Chemokine Testing

  Once per week for four weeks post administration

• Assessment of change in completion time -Six-minute walk test (6MWT)

  Four weeks post administration

• Assessment of Change in Complete blood count with differential (CBC with diff) Laboratory Testing Results

  Each week for four weeks post administration

• Assessment of Change in Lactate dehydrogenase (LDH) Laboratory Testing Results

  Each week for four weeks post administration

• Assessment of Change in Prothrombin time/partial thromboplastin time (PT/PTT Coagulation factors II) Laboratory Testing Results

  Each week for four weeks post administration

Study Arms (2)

ATCell Treatment Group

EXPERIMENTAL

A single administration of expanded autologous lines at a total dose exposure of 150 million cells ("ATCell™") will be administered to this group.

Procedure: Adipose Tissue Harvest; Biological: ATCell

Placebo

PLACEBO COMPARATOR

a single administration of Placebo (Sham Treatment) IV infusion of Ringers Lactate with 5% Dextrose will be administered to this group.

Procedure: Adipose Tissue Harvest

Interventions

Adipose Tissue Harvest PROCEDURE

Local Anesthesia will be administered. A Stab wound will be created at the harvest site through which a 3.0 or 2.5 mm cannula will be inserted to suction fat using the "syringe" (i.e. manual) technique. A total of 100 cc of lipoaspirate will be collected by manual draw of the adipose tissue into syringes.

Also known as: Liposuction

ATCell Treatment Group; Placebo

ATCell BIOLOGICAL

Infusion of the study medication at the rate of 575 mL/HR (500ml of LRD5 plus 75ml of ATCell suspended in LRD5) and continue until all received trial medication has been delivered.

Also known as: Autologous Adipose Derived Mesenchymal Stem Cells

ATCell Treatment Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Active duty service members: military retirees, DEERS eligible dependents who are Tricare beneficiaries only (Department of Defense (DoD) investigational sites only)
• Participants ages of 18 years and above
• Documentation of a positive COVID-19 polymerase chain reaction (PCR) test or strong history of SARS-CoV-2 exposure with positive supportive serology
• Male or female or other gender
• Individuals with established diagnosis of PASC
• Subjects with moderate to severe levels of PASC based on synthesis of multiple assessment modalities provided by the multispecialty study team.
• PASC phenotype to include signs and symptoms of fatigue and low endurance and either Autonomic Disorder or Dyspnea or both.
• Subjects who are able to comprehend the consent procedure and follow the treatment process.
• 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.
• 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 .
• 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.
• 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.
• 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.
• Individuals with the following Vital Signs:
• Systolic Blood Pressure of \> 100 or \< 140 (mmHg)

You may not qualify if:

• Subjects with documented past or current history of severe depression, suicidal ideations or suicidal attempts.
• Subjects who are unable to comprehend the content of informed consent
• Female subjects who are pregnant or who are not willing to practice effective contraception during and for 112 days following the last study visit
• Female subjects who are breastfeeding
• History of abnormal brain or spinal MRI for presence of thromboembolic events.
• Recent traumatic brain injury or other concussive event within 12 months of medical history review
• History of abnormal Echocardiogram for cardiac structure or function in the last 10 years.
• Prior history of postural orthostatic tachycardia syndrome predating diagnosis of SARS-CoV2 infection
• Uncontrolled hypertension or hyperlipidemia
• Prior to COVID diagnosis, the presence of abnormal chest x-ray for any parenchymal disease, or,
• Active tuberculosis or ongoing treatment for tuberculosis or any acute or chronic infection affecting lung
• Chronic lung disease due to fibrosis or autoimmune inflammation such as sarcoidosis or rheumatoid arthritis, vasculitis or lupus
• Lung cancer
• Asthma
• Chronic obstructive pulmonary disease (COPD)

Sponsors & Collaborators

• American CryoStem Corporation: lead

Related Publications (17)

• Nasserie T, Hittle M, Goodman SN. Assessment of the Frequency and Variety of Persistent Symptoms Among Patients With COVID-19: A Systematic Review. JAMA Netw Open. 2021 May 3;4(5):e2111417. doi: 10.1001/jamanetworkopen.2021.11417.

  PMID: 34037731 BACKGROUND

• Alkodaymi MS, Omrani OA, Ashraf N, Shaar BA, Almamlouk R, Riaz M, Obeidat M, Obeidat Y, Gerberi D, Taha RM, Kashour Z, Kashour T, Berbari EF, Alkattan K, Tleyjeh IM. Prevalence of post-acute COVID-19 syndrome symptoms at different follow-up periods: a systematic review and meta-analysis. Clin Microbiol Infect. 2022 May;28(5):657-666. doi: 10.1016/j.cmi.2022.01.014. Epub 2022 Feb 3.

  PMID: 35124265 BACKGROUND

• Carfi A, Bernabei R, Landi F; Gemelli Against COVID-19 Post-Acute Care Study Group. Persistent Symptoms in Patients After Acute COVID-19. JAMA. 2020 Aug 11;324(6):603-605. doi: 10.1001/jama.2020.12603.

  PMID: 32644129 BACKGROUND

• Nehme M, Braillard O, Alcoba G, Aebischer Perone S, Courvoisier D, Chappuis F, Guessous I; COVICARE TEAM. COVID-19 Symptoms: Longitudinal Evolution and Persistence in Outpatient Settings. Ann Intern Med. 2021 May;174(5):723-725. doi: 10.7326/M20-5926. Epub 2020 Dec 8. No abstract available.

  PMID: 33284676 BACKGROUND

• Garrigues E, Janvier P, Kherabi Y, Le Bot A, Hamon A, Gouze H, Doucet L, Berkani S, Oliosi E, Mallart E, Corre F, Zarrouk V, Moyer JD, Galy A, Honsel V, Fantin B, Nguyen Y. Post-discharge persistent symptoms and health-related quality of life after hospitalization for COVID-19. J Infect. 2020 Dec;81(6):e4-e6. doi: 10.1016/j.jinf.2020.08.029. Epub 2020 Aug 25.

  PMID: 32853602 BACKGROUND

• Ladds E, Rushforth A, Wieringa S, Taylor S, Rayner C, Husain L, Greenhalgh T. Persistent symptoms after Covid-19: qualitative study of 114 "long Covid" patients and draft quality principles for services. BMC Health Serv Res. 2020 Dec 20;20(1):1144. doi: 10.1186/s12913-020-06001-y.

  PMID: 33342437 BACKGROUND

• Huang C, Huang L, Wang Y, Li X, Ren L, Gu X, Kang L, Guo L, Liu M, Zhou X, Luo J, Huang Z, Tu S, Zhao Y, Chen L, Xu D, Li Y, Li C, Peng L, Li Y, Xie W, Cui D, Shang L, Fan G, Xu J, Wang G, Wang Y, Zhong J, Wang C, Wang J, Zhang D, Cao B. 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study. Lancet. 2021 Jan 16;397(10270):220-232. doi: 10.1016/S0140-6736(20)32656-8. Epub 2021 Jan 8.

  PMID: 33428867 BACKGROUND

• Jin Y, Ji W, Yang H, Chen S, Zhang W, Duan G. Endothelial activation and dysfunction in COVID-19: from basic mechanisms to potential therapeutic approaches. Signal Transduct Target Ther. 2020 Dec 24;5(1):293. doi: 10.1038/s41392-020-00454-7.

  PMID: 33361764 BACKGROUND

• Bocci M, Oudenaarden C, Saenz-Sarda X, Simren J, Eden A, Sjolund J, Moller C, Gisslen M, Zetterberg H, Englund E, Pietras K. Infection of Brain Pericytes Underlying Neuropathology of COVID-19 Patients. Int J Mol Sci. 2021 Oct 27;22(21):11622. doi: 10.3390/ijms222111622.

  PMID: 34769052 BACKGROUND

• Cardot-Leccia N, Hubiche T, Dellamonica J, Burel-Vandenbos F, Passeron T. Pericyte alteration sheds light on micro-vasculopathy in COVID-19 infection. Intensive Care Med. 2020 Sep;46(9):1777-1778. doi: 10.1007/s00134-020-06147-7. Epub 2020 Jun 12. No abstract available.

  PMID: 32533198 BACKGROUND

• Jones OY, Yeralan S. Is Long COVID a State of Systemic Pericyte Disarray? J Clin Med. 2022 Jan 24;11(3):572. doi: 10.3390/jcm11030572.

  PMID: 35160024 BACKGROUND

• Munir H, McGettrick HM. Mesenchymal Stem Cell Therapy for Autoimmune Disease: Risks and Rewards. Stem Cells Dev. 2015 Sep 15;24(18):2091-100. doi: 10.1089/scd.2015.0008. Epub 2015 Jul 28.

  PMID: 26068030 BACKGROUND

• Mezey E, Nemeth K. Mesenchymal stem cells and infectious diseases: Smarter than drugs. Immunol Lett. 2015 Dec;168(2):208-14. doi: 10.1016/j.imlet.2015.05.020. Epub 2015 Jun 4.

  PMID: 26051681 BACKGROUND

• Arabpour E, Khoshdel S, Tabatabaie N, Akhgarzad A, Zangiabadian M, Nasiri MJ. Stem Cells Therapy for COVID-19: A Systematic Review and Meta-Analysis. Front Med (Lausanne). 2021 Nov 29;8:737590. doi: 10.3389/fmed.2021.737590. eCollection 2021.

  PMID: 34912818 BACKGROUND

• Golchin A, Seyedjafari E, Ardeshirylajimi A. Mesenchymal Stem Cell Therapy for COVID-19: Present or Future. Stem Cell Rev Rep. 2020 Jun;16(3):427-433. doi: 10.1007/s12015-020-09973-w.

  PMID: 32281052 BACKGROUND

• Worm-Smeitink M, Gielissen M, Bloot L, van Laarhoven HWM, van Engelen BGM, van Riel P, Bleijenberg G, Nikolaus S, Knoop H. The assessment of fatigue: Psychometric qualities and norms for the Checklist individual strength. J Psychosom Res. 2017 Jul;98:40-46. doi: 10.1016/j.jpsychores.2017.05.007. Epub 2017 May 8.

  PMID: 28554371 BACKGROUND

• Plash WB, Diedrich A, Biaggioni I, Garland EM, Paranjape SY, Black BK, Dupont WD, Raj SR. Diagnosing postural tachycardia syndrome: comparison of tilt testing compared with standing haemodynamics. Clin Sci (Lond). 2013 Jan;124(2):109-14. doi: 10.1042/CS20120276.

  PMID: 22931296 BACKGROUND

MeSH Terms

Conditions

Post-Acute COVID-19 Syndrome

Interventions

Lipectomy

Condition Hierarchy (Ancestors)

COVID-19; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Post-Infectious Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cosmetic Techniques; Therapeutics; Bariatric Surgery; Bariatrics; Obesity Management; Surgical Procedures, Operative; Plastic Surgery Procedures

Study Officials

• Anthony Y Dudzinski

  American CryoStem Corporation

  STUDY DIRECTOR

Central Study Contacts

Anthony Dudzinski

CONTACT

1-732-747-1007; tdudzinski@americancryostem.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: To ensure proper Randomization, the Sponsor has elected to use the NIH National Cancer Institute Clinical Trial Randomization tool
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: December 21, 2022
• First Posted: December 30, 2022
• Study Start: August 1, 2023
• Primary Completion: December 31, 2023
• Study Completion: February 1, 2024
• Last Updated: June 9, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share