None listed
Conditions
Brief summary
Airways disease such as Chronic Obstructive Pulmonary Disease (COPD) are amongst the top 5 causes of global morbidity and mortality. In Australia, 1 in 10 people above the age of 45 years has COPD and amongst the top 5 most prevalent diseases in Australia. COPD is usually progressive resulting in terminal respiratory failure. Standard therapies include bronchodilators and inhaled corticosteroids. Bronchodilators cause smooth muscle relaxation and may reduce mucus formation. Inhaled corticosteroids reduce eosinophilic inflammation in a cohort of subjects with COPD. Taken together these treatments provide symptomatic relief but do not address the ongoing tissue damage and impaired repair by the disordered immune system. We have demonstrated for the first time in human subjects that intravenous infusions of human mesenchymal stromal cells (MSCs) reduced systemic inflammation by immune-modulating monocytes and increasing anti-inflammatory T regulatory cells. Furthermore, we have shown that the supernatant or conditioned media in which the MSCs are grown in (MSC-CM) have similar immunosuppressive properties. Notably we demonstrated that when the MSC-CM is nebulised, it retained the anti-inflammatory properties. We therefore propose to test the safety and potential efficacy of nebulised conditioned media from MSCs (Neb-MSC-CM) in moderate to severe cohorts of COPD patients and those with frequent exacerbations of COPD. We will assess the safety and efficacy by improvements in quality of life, exercise tolerance and lung function and systemic inflammatory markers. The successful completion of this safety study will then allow us to pursue randomised control trials and commercialisation of this product.
Interventions
Conditioned media from cultures of allogeneic, bone marrow derived, culture expanded, mesenchymal stromal cells will be produced by CTTWA at RPH. Collection, manufacturing and administration of MSC are performed according to Good Manufacturing Practise (GMP) standards, TGA licenced and audited regularly by the TGA.
Patients will receive one dose (5ml) of nebulised mesenchymal stromal cells conditioned media (MSC-CM) on Day 0, administered by A/Prof Yuben Moodley (Respiratory Physician). Durati
Conditioned media from cultures of allogeneic, bone marrow derived, culture expanded, mesenchymal stromal cells will be produced by CTTWA at RPH. Collection, manufacturing and administration of MSC are performed according to Good Manufacturing Practise (GMP) standards, TGA licenced and audited regularly by the TGA. Patients will receive one dose (5ml) of nebulised mesenchymal stromal cells conditioned media (MSC-CM) on Day 0, administered by A/Prof Yuben Moodley (Respiratory Physician). Duration of treatment (nebulisation) take about 5 minutes to complete. One of the identified active anti-inflammatory mediators in MSC-CM is soluble TNF receptor 1 (sTNFR1) present at a concentration of ~50 pg/mL. The level of sTNFR1 will first be measured in the batch of MSC-CM used for this study and all participant will receive the same batch of MSC-CM, hence no adjustment of the inhalant is required between participants.
Sponsors
Institute for Respiratory Health
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Patients with clinical features consistent with COPD - Moderately severe COPD (FEV1 = 40-60% predicted) - Age > 40 years - Provision of written informed consent
Exclusion criteria
Inhaled corticosteroids Malignancy Immunomodulatory treatment Diabetes Severe co-morbidities such as cardiac failure
Outcome results
None listed