Sarcoidosis
Conditions
Brief summary
The purpose of this study is to determine if nicotine treatment is beneficial for the treatment of sarcoidosis. Sarcoidosis is a disease of unknown cause that leads to inflammation. This disease affects your body's organs.
Detailed description
Participants will be randomly divided into two groups. One group will receive a nicotine patch to use for approximately 7 months; the other group will receive placebo for nicotine patches to use for the same time period. Both groups will be contacted weekly by phone for the first 3 weeks then monthly for the duration of the study to monitor for any side effects. The following information and samples will be collected: Questionnaires Medical History Spirometry CT Scans Physical Exam Blood Samples for nicotine and nicotine metabolites
Interventions
DRUGHabitrol
Patch used daily for 28 weeks
DRUGPlacebo to Habitrol
Sponsors
The Cleveland Clinic
Ohio State University
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Adult male and female subjects ≥ 18 to ≤ 75 years of age will be screened for eligibility. * Eligible adult patients will have histologically proven sarcoidosis, diagnosed at least 6 months before screening, evidence of parenchymal disease on chest radiograph, an FVC between 50% and 85% of the predicted value, and a Medical Research Council dyspnea score (47) of at least grade 1. * Patients must have been treated with at least 10 mg/day of prednisone or equivalent or one or more immunomodulating agents (hydroxychloroquine, methotrexate, azathioprine, leflunomide) for \>3 months before screening. * Doses of these medications must be stable for at least 1 month before study entry. * During the study, background medication regimen and doses are to remain stable.
Exclusion criteria
* active tobacco smoking or use of smokeless tobacco products containing nicotine, * active cardiac or central nervous system disease, * history of adverse reaction to nicotine or nicotine-containing products, * patients with extensive irreversible pulmonary fibrosis (based upon lung biopsy or high resolution CT scan criterion) or inability to provide consent. The subject will be excluded if they have a smoking history of greater than 20 pack years, or a diagnosis of other significant respiratory disorder other, than sarcoidosis that, in the opinion of the investigator, would complicate the evaluation of response to treatment; or, history of substance abuse (drugs or alcohol) within 3 years prior to screening or other circumstances (e.g., psychiatric disease) that could interfere with the subject's adherence to protocol requirements or increase their risk of drug (nicotine) dependence.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Forced Vital Capacity (FVC) | 28 weeks | changes in forced vital capacity (FVC) measured by pulmonary function testing (breathing tests) measured in liters |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes Detected by Computed Tomography (CT) of Lungs | 28 weeks | CT lung scans are analyzed by a computer program: Briefly, lung architecture, manifest as pixelated Houndsfield units, is assessed for regional mismatches (texture), wherein linear conformation of pixels are removed (equating with airways, blood or lymphatic vessels) and the mismatched pixels are quantified (i.e., Lung Texture Score; LTS) and are reflective of lung anatomy, including lung nodules, interstitial fibrosis or alveolar ground glass (i.e., pulmonary sarcoidosis manifestations). LTS is represented by arbitrary units, and are reported to range from 25 - 70; 25-40 being within the normal range (i.e., normal lung anatomy; and values in the 40 - 70 range are associated lung parenchymal disease (PMID: 22628482). |
Countries
United States
Participant flow
Recruitment details
January 2015 through January 2019 from The Ohio State University Medical Center and from Cleveland Clinic Foundation
Pre-assignment details
Patients were screened for lung fibrosis and for cardiac involvement of sarcoidosis and were excluded if these were present
Participants by arm
| Arm | Count |
|---|---|
| Habitrol Habitrol Nicotine patch - 7,14,21 mg patches Qd
Habitrol: Patch used daily for 28 weeks | 24 |
| Placebo Placebo patch - 7,14,21 mg patches Qd
Placebo to Habitrol | 26 |
| Total | 50 |
Baseline characteristics
| Characteristic | Habitrol | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 51.8 years STANDARD_DEVIATION 11.5 | 53.9 years STANDARD_DEVIATION 10 | 55.8 years STANDARD_DEVIATION 8 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 16 Participants | 10 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 18 Participants | 34 Participants | 16 Participants |
| Region of Enrollment United States | 24 participants | 50 participants | 26 participants |
| Sex: Female, Male Female | 13 Participants | 30 Participants | 17 Participants |
| Sex: Female, Male Male | 11 Participants | 20 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 0 / 26 |
| other Total, other adverse events | 6 / 24 | 2 / 26 |
| serious Total, serious adverse events | 0 / 24 | 0 / 26 |
Outcome results
Primary
Forced Vital Capacity (FVC)
changes in forced vital capacity (FVC) measured by pulmonary function testing (breathing tests) measured in liters
Time frame: 28 weeks
Population: Change in FVC from baseline to week 28 (study completion) in Habitrol treatment group compared to Placebo treatment group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment | Forced Vital Capacity (FVC) | 0.07 liters | Standard Error 0.22 |
| Control | Forced Vital Capacity (FVC) | -0.07 liters | Standard Error 0.04 |
Secondary
Changes Detected by Computed Tomography (CT) of Lungs
CT lung scans are analyzed by a computer program: Briefly, lung architecture, manifest as pixelated Houndsfield units, is assessed for regional mismatches (texture), wherein linear conformation of pixels are removed (equating with airways, blood or lymphatic vessels) and the mismatched pixels are quantified (i.e., Lung Texture Score; LTS) and are reflective of lung anatomy, including lung nodules, interstitial fibrosis or alveolar ground glass (i.e., pulmonary sarcoidosis manifestations). LTS is represented by arbitrary units, and are reported to range from 25 - 70; 25-40 being within the normal range (i.e., normal lung anatomy; and values in the 40 - 70 range are associated lung parenchymal disease (PMID: 22628482).
Time frame: 28 weeks
Population: Change in lung texture score from baseline to study completion in the Habitrol treatment group compared to the Placebo group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment | Changes Detected by Computed Tomography (CT) of Lungs | -1.0 score on a scale | Standard Deviation 3.5 |
| Control | Changes Detected by Computed Tomography (CT) of Lungs | 2.5 score on a scale | Standard Deviation 3.5 |