Skip to main content
OpenTrials
Completed

NCT Number: NCT03655808

Autologous Transplantation of Bronchial Basal Cells for Treatment of Bronchiectasis

Bronchiectasis is a disease resulted from progressive destruction of bronchi with no effective drug for its treatment. In this study, we intends to carry out a randomized, single-blinded, controlled pilot clinical trial at 1/2 phase. During the process, autologous bronchial basal cells (BBCs) will be dissected from trial tissue via bronchoscopic brushing. Then the BBCs will be expanded and detected by quality control. In the following, qualified BBCs will be injected directly into the lesion by fiberoptic bronchoscopy after airway clearance. The investigators will evaluate the safety and effectiveness of the treatment by measuring a serial of indicators, including occurrence of adverse events, pulmonary function, 6 minute walk distance (6MWD), the distance-saturation product (DSP), St. George's Respiratory Questionnaire (SGRQ), FACED scoring, bronchiectasis severity index (BSI) , and high-resolution computed tomography (HRCT) at week 4, week 12, and week 24 after cell transplantation.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Bronchiectasis Bronchial Diseases Respiratory Tract Diseases

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Ruijin Hospital Shanghai JiaoTong University School of Medicine

Shanghai, Shanghai Municipality, 200025, China

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Subjects diagnosed as bronchiectasis.
  • Subjects with a DLCO < 80% predicted value.
  • Subjects with stable condition for more than 2 weeks.
  • Subjects can do pulmonary function tests.
  • Subjects can tolerate bronchoscopy.
  • Subjects signed informed consent.

Exclusion criteria

  • Women of childbearing age at the stage of pregnancy or lactation, or those without taking effective contraceptive measures.
  • Subjects with positive serological tests for hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV) or syphilis (HBV carriers and patients with stable chronic hepatitis B could be accepted if titers of HBV DNA < 500 IU/mL or copies < 1000 copies/mL; patients with curative hepatitis C were eligible if HCV RNA tests were negative).
  • Subjects with any malignancy.
  • Subjects with any of the following pulmonary diseases: active tuberculosis, pulmonary embolism, pneumothorax, multiple huge bullae, uncontrolled asthma, acute exacerbation of chronic bronchitis or extremely severe COPD.
  • Subjects with other serious diseases, such as poorly controlled diabetes, myocardial infarction, unstable angina, cirrhosis, and acute glomerulonephritis.
  • Subjects with leukopenia (WBC less than 4x10^9 / L) or agranulocytosis (WBC less than 1.5x10^9 / L or neutrophils less than 0.5x10^9 / L) caused by any reason.
  • Subjects with severe renal impairment, serum creatinine> 1.5 times of the upper limit of normal.
  • Subjects with liver disease or liver damage: ALT, AST, total bilirubin> 2 times of the upper limit of normal.
  • Subjects with a history of mental illness or suicide risk, with a history of epilepsy or other central nervous system disorders.
  • Subjects with severe arrhythmias (such as ventricular tachycardia, frequent superventricular tachycardia, atrial fibrillation, and atrial flutter, etc.) or cardiac degree II or above conduction abnormalities displayed via 12-lead ECG.
  • Subjects with a history of alcohol or illicit drug abuse.
  • Subjects accepted by any other clinical trials within 3 months before the enrollment.
  • Subjects with poor compliance, difficult to complete the study.
  • Any other conditions that might increase the risk of subjects or interfere with the clinical trial.

Treatment and study plan

Bronchial basal cells (BBCs)

Biological

Airway epithelial cells were collected in patients of the cell treatment group by a disposable 2-mm brush in order to obtain BBCs. The obtained tissue were washed and enzymatically digested to form a single-cell suspension, which was then cultured under R-Clone system, a patented technique of Regend Therapeutics, Ltd.. For patients in the cell treatment group, on the basis of B-ACT therapy, they were also received autologous BBCs transplantation. Cell suspension was diluted with normal saline. Fibrotic bronchoscopy was guided into the lobular or segmental airways and cells were instilled into lobes.

Other names: P63+ lung stem/progenitor cells, Airway basal cells, Lung stem/progenitor cells

Bronchoscopic airway clearance treatment （B-ACT）

Procedure

The bronchoscopy was performed by board-certified respiratory physicians of Ruijin Hospital using a flexible fiber-optic bronchoscope. B-ACT therapy was performed on all patients in both groups according to the protocol. In brief, continuous suction was performed with the sputum aspirator from the trachea to the subsegmental during the entering of bronchoscope to remove the visible secretions from entire respiratory tract, and then operators used normal saline to collect lavage fluid (the volume various depending on the operator's judgement).

Primary outcomes

  1. Diffusing capacity of the lung for carbon monoxide (DLCO)

    Time frame: Week 4, 12, and 24 after treatment

    An indicator of pulmonary function

Secondary outcomes

  1. Forced expiratory volume measured at the first second (FEV1)

    Time frame: Week 4, 12, and 24 after treatment

    An indicator for pulmonary function test to assess airway obstruction

  2. Forced vital capacity (FVC)

    Time frame: Week 4, 12, and 24 after treatment

    An indicator for pulmonary function test to indicate the maximum amount of air a person can expel from the lungs after a maximum inhalation

  3. The ratio of forced expiratory volume in the first one second to the forced vital capacity (FEV1/FVC)

    Time frame: Week 4, 12, and 24 after treatment

    An indicator in pulmonary function test to represent the proportion of a person's vital capacity that they are able to expire in the first second of forced expiration to the full vital capacity

  4. Maximum Mid Expiratory Flow (MMEF)

    Time frame: Week 4, 12, and 24 after treatment

    An indicator in pulmonary function test to stand for maximal (mid-)expiratory flow and is the peak of expiratory flow as taken from the flow-volume curve and measured in liters per second

  5. Maximum Voluntary Ventilation (MVV)

    Time frame: Week 4, 12, and 24 after treatment

    An indicator in pulmonary function test to measure the maximum amount of air that can be inhaled and exhaled within one minute

  6. 6 minute walk distance (6MWD) and distance saturation product (DSP)

    Time frame: Week 4, 12, and 24 after treatment

    An indicator for heart and pulmonary function

  7. St. George's Respiratory Questionnaire (SGRQ)

    Time frame: Week 4, 12, and 24 after treatment

    An indicator to measure health status (quality of life) in patients with diseases of airways obstruction

  8. FACED scoring

    Time frame: Week 4, 12, and 24 after treatment

    An assessment of severity tool, validated for people with non-cystic fibrosis bronchiectasis. F means "FEV1", A means "Age", C means "Chronic colonization", E means "Extension", D means "Dyspnoea".

  9. Bronchiectasis Severity Index (BSI)

    Time frame: Week 4, 12, and 24 after treatment

    A combination of clinical, radiological and microbiological features to predict morbidity and mortality.

  10. High resolution computed tomography (HR-CT) imaging of lung

    Time frame: Week 4, 12, and 24 after treatment

    An indicator for analysis of dilated bronchi, HR-CT images of lung will be analyzed to indicate the pulmonary structure

  11. Safety outcomes: adverse events

    Time frame: Through study completion, an average of 24 weeks

    Any unexpected and unfavorable medical occurrence related to any medical intervention in the study

Sponsors and collaborators

Lead sponsor

Ruijin Hospital

Other

Collaborators

  • Regend Therapeutics

Registry information

Important dates

Study start
2020
Primary completion
2023
Study completion
2023
First posted
Aug 31, 2018
Registry last updated
Dec 5, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.