Targeting Oxidative Stress in Chronic Beryllium Disease

NCT01088243 | Completed Phase 1 Results DMC

• 1 other identifier: HS-2360B
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to understand if a drug called mesalamine helps to control inflammation associated with chronic beryllium disease (CBD). We hypothesize that in CBD subjects treated with prednisone, mesalamine treatment will enhance the immunosuppressive effects of prednisone, and thus reduce the immune response to beryllium.

Conditions

Chronic Beryllium Disease

Keywords

Berylliosis; Beryllium Disease

Outcome Measures

Primary Outcomes (1)

• Change in Beryllium Lymphocyte Proliferation Responses (BeLPT) From Baseline to Week 6

  Primary endpoints are beryllium proliferation responses (BeLPT) in PBMCs (peripheral blood mononuclear cells) and BAL (bronchoalveolar lavage) cells. The BeLPT is a blood test that measures the immune response to beryllium exposure. If immune cells multiply in response to beryllium, this is considered an abnormal test results. If immune cells do not multiple, this is considered a normal test results. Results are reported as "stimulation index", which is a ratio of the number of cells grown with beryllium compared to the number of cells grown without beryllium. A value of 2.5 or less is considered normal, and a value greater than 2.5 is abnormal.

  baseline and week 6

Secondary Outcomes (5)

• Changes in Bronchoalveolar Lavage (BAL) Tumor Necrosis Factor Alpha (TNFa)

  baseline and week 6

• Changes in Steady-state Glutathione (GSH) Levels From Baseline to Week 6

  baseline and week 6

• HDAC2 Levels

  baseline and week 6

• Glucocorticoid Receptors

  baseline and week 6

• Lung Function

  baseline and week 6

Study Arms (2)

Mesalamine

EXPERIMENTAL

Mesalamine (5-ASA) 500 mg capsules four times per day for 6 weeks in Chronic Beryllium Disease subjects.

Drug: Mesalamine

Placebo

PLACEBO COMPARATOR

Sugar pill 500 mg capsules four times per day for 6 weeks in Chronic Beryllium Disease subjects.

Drug: Placebo

Interventions

Mesalamine DRUG

Mesalamine (5-ASA) 500 mg capsules four times per day for 6 weeks in Chronic Beryllium Disease subjects.

Also known as: Pentasa, 5-ASA

Mesalamine

Placebo DRUG

Sugar pill 500 mg capsules four times per day for 6 weeks in Chronic Beryllium Disease subjects.

Also known as: Sugar Pill

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of chronic beryllium disease based on the criteria below:
• History of beryllium exposure, and;
• Positive blood and/or bronchoalveolar lavage Beryllium Lymphocyte Proliferation Tests (BeLPT), and;
• Biopsy-proven pathologic changes consistent with CBD-non-caseating granulomas and/or mononuclear cell interstitial infiltrates, and;
• Positive bronchoalveolar lavage (BAL) BeLPT and \> 15% lymphocytes in BAL fluid.

You may not qualify if:

• History of Hepatic disease
• History of Renal disease
• Hypersensitivity to Pentasa (5-ASA) or salicylates.
• Pregnancy
• Presence of another disease that may be expected to significantly affect patient mortality (e.g., HIV), severe cor pulmonale);
• The use of blood thinners.
• Current use of tobacco (smoking or otherwise) in the past 6 months
• If undergoing bronchoscopy:
• Severe room air hypoxemia (precluding transbronchial lung biopsy and/or BAL), e.g., pO2 \< 45 (Denver altitude 5,280 feet);

Sponsors & Collaborators

• National Jewish Health: lead

Study Sites (1)

National Jewish Health

Denver, Colorado, 80206, United States

Location

MeSH Terms

Conditions

Berylliosis

Interventions

Mesalamine; Sugars

Condition Hierarchy (Ancestors)

Pneumoconiosis; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Lung Injury; Occupational Diseases

Intervention Hierarchy (Ancestors)

meta-Aminobenzoates; Aminobenzoates; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Aminosalicylic Acids; Salicylates; Hydroxybenzoates; Hydroxy Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenols; Carbohydrates

Results Point of Contact

• Title: Dr. Lisa A. Maier
• Organization: National Jewish Health

MaierL@NJHealth.org

303-398-1983

Study Officials

• Lisa A. Maier, M.D., MSPH

  National Jewish Health

  PRINCIPAL INVESTIGATOR

• Brian Day, PhD

  National Jewish Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: March 15, 2010
• First Posted: March 17, 2010
• Study Start: March 1, 2010
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: October 12, 2018
• Results First Posted: December 12, 2017

Record last verified: 2018-09

Locations

US (1)