Chronic Beryllium DiseasePhase 1/2NCT01088243

Targeting Oxidative Stress in Chronic Beryllium Disease

A Phase 1/2 study testing Mesalamine in people with Chronic Beryllium Disease, run by National Jewish Health at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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… Read more about this study

Who is it for?: Ages 18 to 80 years
Conditions the study is for: Chronic Beryllium Disease
What is being tested?: Mesalamine
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 18 participants
Where: 1 siteUnited States
Study dates: Mar 2010to Mar 2015
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 80 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

Show all 10Show fewer

Current use of tobacco (smoking or otherwise) in the past 6 months
Patient inability to participate in the study, such as inability to undergo venipuncture and BAL procedures (if undergoing bronchoscopy) that form part of the inclusion/exclusion criteria or part of the outcome measure.
If undergoing bronchoscopy:
Severe room air hypoxemia (precluding transbronchial lung biopsy and/or BAL), e.g., pO2 < 45 (Denver altitude 5,280 feet);

Trial locations and contacts

1 site in 1 country.

United States1 site

National Jewish Health
Denver, Colorado, 80206

Other trials in United States

About this study

Read the detailed description

The overall goal of this study is to understand the role of oxidative stress as a potential therapeutic target in the pathogenesis of chronic beryllium disease (CBD). CBD is an inflammatory hypersensitivity lung disease that occurs in an estimated 800,000 beryllium-exposed workers in the United Sates. CBD is characterized by the presence of pulmonary non-caseating granulomas with accumulation of macrophages and beryllium specific CD4+ T cells (Newman et al. 1998). Upon beryllium stimulation in vitro, beryllium specific CD4+ T cells proliferate and produce Th1 cytokines (i.e. TNF-α, IFN-γ, and IL-2) at unusually high levels (Tinkle et al. 1997). The molecular mechanism(s) by which beryllium regulates the chronic production of these cytokines is unknown. Exciting preliminary studies indicate that beryllium alters the redox status of T cells which may adversely modulate the immune response in CBD. Based on these points, a novel hypothesis is proposed: 1) oxidative stress enhances the T cells response to antigen and this enhancement may explain both the excessive cytokine response and the pathogenesis of pulmonary granulomas in CBD and; 2) an inherent difference in T cell antioxidant status is a critical factor in the pathogenesis of CBD. This proposal is a pilot clinical trial examining an approved drug for the treatment of ulcerative colitis (5-amino salicylic acid, 5-ASA), which has anti-inflammatory and antioxidant properties, as a potential new approach for CBD treatment. In this clinical trial, 40 CBD subjects already treated with prednisone, will be treated with either placebo or 5-ASA to determine it effects on the beryllium stimulated immune response in the lung by undergoing bronchoscopy with bronchoalveolar lavage and in blood by undergoing venipuncture before and after 6 weeks of treatment with 5-ASA. As a secondary outcome, we will also assess subjects clinical response to this short course of 5-ASA using spirometry. Bronchoscopies are optional. Patients have the option to participate by undergoing venipuncture and lung function tests only.

Conditions: Chronic Beryllium Disease
Being tested: Mesalamine, Placebo
Keywords: Berylliosis, Beryllium Disease
Medical subject headings: Berylliosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

MesalamineDrug
Also called Pentasa, 5-ASA
Mesalamine (5-ASA) 500 mg capsules four times per day for 6 weeks in Chronic Beryllium Disease subjects.
PlaceboDrug
Also called Sugar Pill
Sugar pill 500 mg capsules four times per day for 6 weeks in Chronic Beryllium Disease subjects.

Study groups in NCT01088243
Study group	Role	What they receive
Mesalamine	Experimental	Mesalamine (5-ASA) 500 mg capsules four times per day for 6 weeks in Chronic Beryllium Disease subjects. Receives: Drug: Mesalamine
Placebo	Placebo comparator	Sugar pill 500 mg capsules four times per day for 6 weeks in Chronic Beryllium Disease subjects. Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: baseline and week 6

Secondary outcomes (5)

Changes in Bronchoalveolar Lavage (BAL) Tumor Necrosis Factor Alpha (TNFa)
Secondary outcomes include changes in bronchoalveolar lavage (BAL) tumor necrosis factor alpha (TNFa)
Measured: baseline and week 6
Changes in Steady-state Glutathione (GSH) Levels From Baseline to Week 6
Secondary outcomes include changes in steady-state GSH levels in beryllium specific CD4+ T cell in bronchoalveolar lavage fluid (BALF)
Measured: baseline and week 6
HDAC2 Levels
Secondary outcomes include changes in HDAC2 levels
Measured: baseline and week 6
Glucocorticoid Receptors
Secondary outcomes include changes in glucocorticoid receptors modification in PBMCs and BAL cells.
Measured: baseline and week 6
Lung Function
Secondary outcomes include changes in lung function, which will be assessed with Forced expiratory volume in 1 second percent predicted (FEV1), Forced vital capacity percent predicted (FVC) and Diffusing capacity percent predicted (DLCO).
Measured: baseline and week 6

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Mar 2010Mar 2015

First posted17 Mar 2010 (estimated)
Study startMar 2010
Primary completionMar 2015
Study completionMar 2015

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Chronic Beryllium DiseaseStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 18 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01088243
Sponsor's protocol ID: HS-2360B
Status last verified: Sep 2018
First submitted: 15 Mar 2010
Last updated: 12 Oct 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Study at a glance

From the registry record, last updated by the sponsor on 12 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Targeting Oxidative Stress in Chronic Beryllium Disease
ClinicalTrials.gov ID: NCT01088243
Acronym / sponsor ID: HS-2360B
Conditions: Chronic Beryllium Disease
Keywords: Berylliosis, Beryllium Disease
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 18 participants (actual)
Lead sponsor: National Jewish HealthUniversity, hospital or other
Study start: Mar 2010
Primary completion: Mar 2015 (actual)
Study completion: Mar 2015 (actual)
First posted: 17 Mar 2010 (estimated)
Results: Posted 12 Dec 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Mesalamine	Experimental	Drug: MesalamineMesalamine (5-ASA) 500 mg capsules four times per day for 6 weeks in Chronic Beryllium Disease subjects.
Placebo	Placebo comparator	Drug: PlaceboSugar pill 500 mg capsules four times per day for 6 weeks in Chronic Beryllium Disease subjects.

Who may qualify

Ages: 18 to 80 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

Diagnosis of chronic beryllium disease based on the criteria below:

Key exclusion criteria (10 listed)

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);

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
MesalamineAlso: Pentasa, 5-ASAMesalamine (5-ASA) 500 mg capsules four times per day for 6 weeks in Chronic Beryllium Disease subjects.	Drug	Mesalamine
PlaceboAlso: Sugar PillSugar pill 500 mg capsules four times per day for 6 weeks in Chronic Beryllium Disease subjects.	Drug	Placebo

Primary outcome

Change in Beryllium Lymphocyte Proliferation Responses (BeLPT) From Baseline to Week 6
Time frame: baseline and 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.

5 secondary outcomes

Changes in Bronchoalveolar Lavage (BAL) Tumor Necrosis Factor Alpha (TNFa)
Time frame: baseline and week 6
Changes in Steady-state Glutathione (GSH) Levels From Baseline to Week 6
Time frame: baseline and week 6
HDAC2 Levels
Time frame: baseline and week 6
Glucocorticoid Receptors
Time frame: baseline and week 6
Lung Function
Time frame: baseline and week 6

Results and safety

Results posted to the registry on 12 Dec 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Mesalamine	13	12
Placebo	5	5

Primary outcome: Change in Beryllium Lymphocyte Proliferation Responses (BeLPT) From Baseline to Week 6

Time frame: baseline and week 6. Mean (Standard Deviation). Unit: Stimulation index

Measure	Mesalamine n = 13	Placebo n = 5
BAL	48.61 (57.18)	9.33 (14.08)
PBMC	22.07 (20.30)	3.8 (6.09)

Population analysed: Because bronchoscopy was not required for participation, only three placebo and six 5-ASA-treated subjects underwent bronchoscopy and is reported under BAL.

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: The patients will be monitored after baseline evaluation, during drug therapy, and after 2 week follow-up evaluation by a study coordinator and Dr. Maier who will follow-up for adverse events at each visit. All adverse events (serious and moderate/mild) associated with bronchoscopy procedures and study drug will be assessed individually by study PIs for appropriate action if necessary.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Mesalamine	0 of 13 (0%)	2 of 13 (15.4%)	Not reported
Placebo	0 of 5 (0%)	2 of 5 (40%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 12 Oct 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Lisa A. Maier, M.D., MSPH principal investigator

National Jewish Health

Brian Day, PhD principal investigator

National Jewish Health

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Mesalamine in people with Chronic Beryllium Disease, run by National Jewish Health at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Dec 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Beryllium Lymphocyte Proliferation Responses (BeLPT) From Baseline to Week 6 (time frame: baseline and week 6). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01088243.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Oct 2018.