Nebulized PL for Post-COVID-19 Syndrome

Covid19 Clinical Trial

Official title:

Autologous Nebulized Platelet Lysate for Post COVID-19 Syndrome

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04487691
• Other study ID #: RGX2020-RCT01
• Status: Terminated
• Phase: N/A
• Start date: December 8, 2020
• Est. completion date: June 15, 2021

Study information

• Verified date: January 2022
• Source: Regenexx, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To evaluate and compare nebulized platelet lysate to placebo control of saline administered via handheld nebulizer 1x daily for eight weeks to determine effect on lung function in patients with post-COVID-19 ARDS syndrome.

Description:

This is a double-blind, randomized, placebo controlled single-center study using nebulized platelet lysate compared to placebo control of saline administered via handheld nebulizer 1x daily for eight weeks to determine effect on lung function in patients with post-COVID-19 ARDS syndrome.

20 patients randomized to Treatment group: Inhaled nebulized platelet lysate (PL) 1x daily for eight weeks 20 patients randomized to Control group: Inhaled nebulized saline, 1x daily for eight weeks.

Outcomes will be measured at 4-weeks, 8-weeks, 3-months, 6- months

Goals for this study are as follows:

1. Investigate and compare the efficacy of autologous PL inhaled via handheld ultrasonic nebulizer, 2-ml once per day for 4-weeks compared to saline control (Phase 1), early treatment timepoint.

2. Investigate and compare the efficacy of autologous PL inhaled via handheld ultrasonic nebulizer, 2-ml once per day for 8-weeks compared to saline control (Phase 1), final treatment timepoint.

3. Investigate, compare, and monitor long term function and quality of life through 6-months for treatment arm compared to control.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: June 15, 2021
• Est. primary completion date: June 15, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

1. Voluntary signature of the IRB approved Informed Consent

2. At least 4-weeks post ventilator or oxygen dependent ARDS treated for at least 48 hours in the ICU

3. Patient is stable enough to have been discharged home

4. Male or female ages 18-85

5. Two weeks to 1-year post hospital discharge

6. Ongoing activity intolerance due to dyspnea related to ARDS

7. Is independent, ambulatory, and can comply with all post-operative evaluations and visits

8. 6-minute walk test distance of < 450 M

9. SF-36 physical component score < 60

10. ARDS caused by viral pneumonia including COVID-19 confirmed through an RNA anti-body test

11. Normal to mild post-ARDS reactive airway disease

Exclusion Criteria:

1. Oxygen dependent on nasal canula greater than 2-L per minute

2. Dependent on inhaled corticosteroid at the discretion of the physician

3. Unable to complete any of the outcomes measured (Spirometry, 6MWD, SF-36, etc.)

4. Active known secondary bacterial or viral infection

5. Active moderate or severe post-ARDS reactive airway disease at the discretion of the physician

6. Pre-morbid COPD

7. Medication list will be reviewed on a case by case basis to allow for flexibility as post-COVID-19 patients' medication list may vary

8. Other medical comorbidities/conditions that may preclude participation in the study

Related Conditions & MeSH terms

• COVID-19
• Covid19

Intervention

Biological:
• Nebulized Platelet Lysate
Approximately 520 cc of autologous venous blood (within AABB guideline limits) will be drawn and platelet lysate (PL), maximizing the patients baseline platelet levels (~2-4x baseline) will be produced in a clean room setting using the Regenexx, LLC proprietary lab protocols (PL-M) utilizing a double lysis technique. From that sample, a high growth factor lysate will be created using a double lysis technique, and a sample will be retained to quantify the protein profile of the PL via ELISA quantitative analysis. The PL will be aliquoted into 56 (n=28x2) 2-ml ampules using sterile technique which will then be frozen at -20°C. The patient will unfreeze each ampule and place it into a handheld ultrasonic nebulizer and inhale the platelet lysate following the nebulizer manufacture's protocol until the treatment is completed. The treatment will be applied once a day for 8-weeks.

Other:
• Nebulized Sterile Saline
Approximately 520 cc of autologous venous blood (within AABB guideline limits) will be drawn and donated for research purposes to keep patient blinded to group allocation. Sterile normal saline to mimic the appearance of the platelet lysate will be aliquoted into 56 (n=28x2) 2-ml ampules using sterile technique which will then be frozen at -20°C. The patient will unfreeze each ampule and place it into a handheld ultrasonic nebulizer and inhale the sterile saline following the nebulizer manufacture's protocol until the treatment is completed. The treatment will be applied once a day for 8-weeks.

Locations

Country	Name	City	State
United States	Centeno-Schultz Clinic	Broomfield	Colorado

Sponsors (1)

Lead Sponsor	Collaborator
Regenexx, LLC

Country where clinical trial is conducted

United States, 

References & Publications (9)

Centeno C, Markle J, Dodson E, Stemper I, Hyzy M, Williams C, Freeman M. The use of lumbar epidural injection of platelet lysate for treatment of radicular pain. J Exp Orthop. 2017 Nov 25;4(1):38. doi: 10.1186/s40634-017-0113-5. — View Citation

Chan KS, Pfoh ER, Denehy L, Elliott D, Holland AE, Dinglas VD, Needham DM. Construct validity and minimal important difference of 6-minute walk distance in survivors of acute respiratory failure. Chest. 2015 May;147(5):1316-1326. doi: 10.1378/chest.14-1808. — View Citation

Del Fante C, Perotti C, Bonferoni MC, Rossi S, Sandri G, Ferrari F, Scudeller L, Caramella CM. Platelet lysate mucohadesive formulation to treat oral mucositis in graft versus host disease patients: a new therapeutic approach. AAPS PharmSciTech. 2011 Sep;12(3):893-9. doi: 10.1208/s12249-011-9649-3. Epub 2011 Jul 6. — View Citation

Geiger S, Hirsch D, Hermann FG. Cell therapy for lung disease. Eur Respir Rev. 2017 Jun 28;26(144). pii: 170044. doi: 10.1183/16000617.0044-2017. Print 2017 Jun 30. Review. — View Citation

Hopkins RO, Weaver LK, Collingridge D, Parkinson RB, Chan KJ, Orme JF Jr. Two-year cognitive, emotional, and quality-of-life outcomes in acute respiratory distress syndrome. Am J Respir Crit Care Med. 2005 Feb 15;171(4):340-7. Epub 2004 Nov 12. — View Citation

Mammoto T, Chen Z, Jiang A, Jiang E, Ingber DE, Mammoto A. Acceleration of Lung Regeneration by Platelet-Rich Plasma Extract through the Low-Density Lipoprotein Receptor-Related Protein 5-Tie2 Pathway. Am J Respir Cell Mol Biol. 2016 Jan;54(1):103-13. doi: 10.1165/rcmb.2015-0045OC. — View Citation

Prem K, Liu Y, Russell TW, Kucharski AJ, Eggo RM, Davies N; Centre for the Mathematical Modelling of Infectious Diseases COVID-19 Working Group, Jit M, Klepac P. The effect of control strategies to reduce social mixing on outcomes of the COVID-19 epidemic in Wuhan, China: a modelling study. Lancet Public Health. 2020 May;5(5):e261-e270. doi: 10.1016/S2468-2667(20)30073-6. Epub 2020 Mar 25. Erratum in: Lancet Public Health. 2020 May;5(5):e260. — View Citation

Rubio MM. (2019). Beyond the Ordinary: The Effect of Cellular Therapy on Quality of Life in Chronic Lung Disease. J Clin Res Med. 2(4): 1-8. https://researchopenworld.com/beyond-the-ordinary-the-effect-of-cellular-therapy-on-quality-of-life-in-chronic-lung-disease/ Accessed 3/27/20.

Salama SM, Kamel IH, Ghanim M, Elsherif A. (2019). The Efficacy of Autologous Nebulized Platelet Rich Plasma (PRP) As an Early Adjuvant Therapeutic and Prognostic Treatment Modality in the Management of Inhalation Lung Injury. Egypt, J Plast Reconstr Surg. 43: 203-208. 10.21608/ejprs.2019.65115

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Spirometry-FVC and FEV1/FVC tests	Changes in pre and post treatment spirometry measures	4 weeks; 8 weeks
Secondary	Spirometry-FVC and FEV1/FVC tests	Changes from pre and post treatment spirometry measures	3 months, 6 months
Secondary	6 Minute Walk Distance test (6MWD)	Changes in distance walked during 6MWD test from pre to post treatment	4 weeks; 8 weeks; 3 months; 6 months
Secondary	Distance-desaturation product from 6MWD	Changes in distance-desaturation product from 6MWD from pre to post treatment	4 weeks; 8 weeks; 3 months; 6 months
Secondary	San Diego Shortness of Breath Questionnaire (SOBQ)	Changes in San Diego Shortness of Breath Questionnaire (SOBQ) score from pre to post; treatment; scores range from 0-120 with higher scores equaling greater breathing impairment	4 weeks; 8 weeks; 3 months; 6 months
Secondary	Short Form-36 (SF-36)	Changes in SF-36 scores from pre to post treatment; 8 subscales 0-100 range where lower scores equal more disability	4 weeks; 8 weeks; 3 months; 6 months
Secondary	Modified Single Assessment Numeric Evaluation (SANE)	Average SANE score post treatment; scores range from 0-100 where 0=no improvement and 100=100% improvement in breathing condition	4 weeks; 8 weeks; 3 months; 6 months
Secondary	Medications	changes in medications from pre to post treatment	4 weeks; 8 weeks; 3 months; 6 months
Secondary	Incidence of adverse events	Incidence of adverse events after treatment	4 weeks; 8 weeks; 3 months; 6 months
Secondary	Incidence of surgical/other treatment interventions	Incidence of surgical/other treatment interventions after treatment	4 weeks; 8 weeks; 3 months; 6 months