Anti-inflammatory Effects of Tiotropium in Patients with Stable COPD

NCT04061161 | Completed Phase 4

• 1 other identifier: 2018-002173-22
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 2

Brief Summary

This study aims to assess the anti-inflammatory effects after 6 weeks treatment with tiotropium compared to placebo in patients with stable COPD

Conditions

COPD

Keywords

Tiotropium; Anti-inflammatory effects; TNF-alpha mRNA in induced sputum

Outcome Measures

Primary Outcomes (1)

• Change in concentration of TNF-alpha (mRNA level) in induced sputum

  To assess whether 6 weeks treatment with tiotropium elicts anti-inflammatory effects compared to placebo in patients with stable COPD, as measured by a change in TNF-alpha mRNA level in induced sputum

  6 week treatment duration

Secondary Outcomes (7)

• Change in concentration of sputum cell differentials in induced sputum

  6 week treatment duration

• Change in concentration of LTB4 level in induced sputum

  6 week treatment duration

• Change in concentration of cytokine protein level in induced sputum

  6 week treatment duration

• Change in concentration of cytokine mRNA level in induced sputum

  6 week treatment duration

• Change in concentration of cell differentials + CRP in blood serum

  6 week treatment duration

Other Outcomes (1)

• Differences in gene expression measured in sputum samples

  6 week treatment duration

Study Arms (2)

Tiotropium respimat

ACTIVE COMPARATOR

Tiotropium respimat 2.5mcg two actuations once daily

Drug: Tiotropium Bromide

Placebo respimat

PLACEBO COMPARATOR

Placebo respimat two actuations once daily

Drug: Tiotropium Bromide

Interventions

Tiotropium Bromide DRUG

Participants will be double-blind randomized for Tiotropium or Placebo treatment for 6 weeks

Placebo respimat; Tiotropium respimat

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men or women, age \>= 40 years.
• A diagnosis of COPD according to the criteria of the GOLD organization
• Post-bronchodilator FEV1 / FVC ratio \< 70% (ERS equations) and post-bronchodilator FEV1 \< 80%pred.
• A smoking history of \> 10 pack years.
• post-bronchodilator FEV1 \> 1.5 Litres and ability to produce sputum after hypertonic saline induction.
• No upper or lower respiratory tract infection in the last 4 weeks necessitating antibiotic treatment or consisting of quite probable viral etiology.
• Being in a stable phase of COPD, as judged by the investigator. No courses of systemic steroids or antibiotics for respiratory problems last 4 weeks
• The participant needs to be able to understand the Dutch language
• Signed and dated informed consent obtained before any study related procedures (including withdrawal of concomitant medication) are conducted.

You may not qualify if:

• Treatment with immune-modulating agents for any disease, including leuktriene receptor antagonists,
• Treatment with long-acting anticholinergics \<4 weeks before the start of the study.
• Treatment with corticosteroids \<4 weeks before the start of the study.
• Targeted lung denervation therapy in the past.
• Concomitant diagnosis of asthma.
• Any significant other pulmonary disease or disorder (e.g. known alpha1-antitrypsine deficiency, significant bronchiectasis), as judged by the investigator.
• Narrow angle glaucoma.
• Azithromycine maintenance treatment.
• Active malignant disease (at least 5 years malignant disease-free)
• Other significant disease or disorder (like cardiovascular, gastrointestinal, liver, renal, neurological, musculoskeletal, endocrine, metabolic (including diagnosed diabetes), malignant, psychiatric, major physical impairment), which, in the opinion of the investigators may either put the patient at risk because of participation in the study, or may influence the results of the study, or the patient's ability to participate in the study.
• Females of childbearing potential without an efficient contraception unless they meet the following definition of post-menopausal: 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum FSH \>40 mIU/mL or the use of one or more of the following acceptable methods of contraception:
• Surgical sterilization (e.g. bilateral tubal ligation, hysterectomy).
• Hormonal contraception (implantable, patch, oral, injectable).
• Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/cream/suppository.
• Continuous abstinence.

Sponsors & Collaborators

• University Medical Center Groningen: lead
• Boehringer Ingelheim: collaborator

Study Sites (2)

University Medical Center

Groningen, 9713 GZ, Netherlands

Location

Medical centrum Leeuwarden

Leeuwarden, 8934 AD, Netherlands

Location

Related Publications (12)

• Bathoorn E, Liesker J, Postma D, Koeter G, van Oosterhout AJ, Kerstjens HA. Safety of sputum induction during exacerbations of COPD. Chest. 2007 Feb;131(2):432-8. doi: 10.1378/chest.06-2216.

  PMID: 17296644 BACKGROUND

• Brightling CE, Monterio W, Green RH, Parker D, Morgan MD, Wardlaw AJ, Pavord D. Induced sputum and other outcome measures in chronic obstructive pulmonary disease: safety and repeatability. Respir Med. 2001 Dec;95(12):999-1002. doi: 10.1053/rmed.2001.1195.

  PMID: 11778799 BACKGROUND

• Gosens R, Zaagsma J, Meurs H, Halayko AJ. Muscarinic receptor signaling in the pathophysiology of asthma and COPD. Respir Res. 2006 May 9;7(1):73. doi: 10.1186/1465-9921-7-73.

  PMID: 16684353 BACKGROUND

• Kerstjens HA, Engel M, Dahl R, Paggiaro P, Beck E, Vandewalker M, Sigmund R, Seibold W, Moroni-Zentgraf P, Bateman ED. Tiotropium in asthma poorly controlled with standard combination therapy. N Engl J Med. 2012 Sep 27;367(13):1198-207. doi: 10.1056/NEJMoa1208606. Epub 2012 Sep 2.

  PMID: 22938706 BACKGROUND

• Kistemaker LE, Bos IS, Menzen MH, Maarsingh H, Meurs H, Gosens R. Combination therapy of tiotropium and ciclesonide attenuates airway inflammation and remodeling in a guinea pig model of chronic asthma. Respir Res. 2016 Feb 4;17:13. doi: 10.1186/s12931-016-0327-6.

  PMID: 26846267 BACKGROUND

• Kistemaker LE, Gosens R. Acetylcholine beyond bronchoconstriction: roles in inflammation and remodeling. Trends Pharmacol Sci. 2015 Mar;36(3):164-71. doi: 10.1016/j.tips.2014.11.005. Epub 2014 Dec 13.

  PMID: 25511176 BACKGROUND

• Kistemaker LE, Oenema TA, Meurs H, Gosens R. Regulation of airway inflammation and remodeling by muscarinic receptors: perspectives on anticholinergic therapy in asthma and COPD. Life Sci. 2012 Nov 27;91(21-22):1126-33. doi: 10.1016/j.lfs.2012.02.021. Epub 2012 Mar 3.

  PMID: 22406302 BACKGROUND

• Perng DW, Tao CW, Su KC, Tsai CC, Liu LY, Lee YC. Anti-inflammatory effects of salmeterol/fluticasone, tiotropium/fluticasone or tiotropium in COPD. Eur Respir J. 2009 Apr;33(4):778-84. doi: 10.1183/09031936.00115308. Epub 2009 Jan 7.

  PMID: 19129278 BACKGROUND

• Powrie DJ, Wilkinson TM, Donaldson GC, Jones P, Scrine K, Viel K, Kesten S, Wedzicha JA. Effect of tiotropium on sputum and serum inflammatory markers and exacerbations in COPD. Eur Respir J. 2007 Sep;30(3):472-8. doi: 10.1183/09031936.00023907. Epub 2007 May 15.

  PMID: 17504798 BACKGROUND

• Tashkin DP, Celli B, Senn S, Burkhart D, Kesten S, Menjoge S, Decramer M; UPLIFT Study Investigators. A 4-year trial of tiotropium in chronic obstructive pulmonary disease. N Engl J Med. 2008 Oct 9;359(15):1543-54. doi: 10.1056/NEJMoa0805800. Epub 2008 Oct 5.

  PMID: 18836213 BACKGROUND

• "Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease 2017 Report: GOLD Executive Summary." Claus F. Vogelmeier, Gerard J. Criner, Fernando J. Martinez, Antonio Anzueto, Peter J. Barnes, Jean Bourbeau, Bartolome R. Celli, Rongchang Chen, Marc Decramer, Leonardo M. Fabbri, Peter Frith, David M.G. Halpin, M. Victorina Lopez Varela, Masaharu Nishimura, Nicolas Roche, Roberto Rodriguez-Roisin, Don D. Sin, Dave Singh, Robert Stockley, Jorgen Vestbo, Jadwiga A. Wedzicha and Alvar Agusti. Eur Respir J 2017; 49: 1700214. Eur Respir J. 2017 Jun 22;49(6):1750214. doi: 10.1183/13993003.50214-2017. Print 2017 Jun. No abstract available.

  PMID: 28642306 BACKGROUND

• Vogelmeier C, Hederer B, Glaab T, Schmidt H, Rutten-van Molken MP, Beeh KM, Rabe KF, Fabbri LM; POET-COPD Investigators. Tiotropium versus salmeterol for the prevention of exacerbations of COPD. N Engl J Med. 2011 Mar 24;364(12):1093-1103. doi: 10.1056/NEJMoa1008378.

  PMID: 21428765 BACKGROUND

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Tiotropium Bromide

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Scopolamine Derivatives; Tropanes; Azabicyclo Compounds; Aza Compounds; Organic Chemicals; Alkaloids; Heterocyclic Compounds; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring

Study Officials

• Wouter van Geffen, MD PhD

  Medical centrum Leeuwarden, Department of pulmonology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Full professor pulmonology; Head of department of Pulmonology and Tuberculosis; Principal Investigator

Model Details: This will be a multicenter parallel design randomized placebo controlled double-blinded study.

Study Record Dates

• First Submitted: August 14, 2019
• First Posted: August 19, 2019
• Study Start: August 19, 2019
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2023
• Last Updated: September 25, 2024

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

NL (2)