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Investigation of the Efficacy of Metformin Therapy on Pulmonary Sarcoidosis (MetforminTOP)

Primary Purpose

Sarcoidosis, Pulmonary

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Metformin
Cellulose
Sponsored by
University of Maryland, Baltimore
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sarcoidosis, Pulmonary

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Patients with sarcoidosis as defined by the ATS/ERS/WASOG statement on sarcoidosis as defined by the clinical presentation consistent with sarcoidosis, as well as biopsy demonstrating granulomas, and no alternative for the cause of the granulomas, such as tuberculosis for at least one year prior to randomization. Tuberculosis must be ruled out by negative histology and culture. Patients must be symptomatic of pulmonary sarcoidosis with FVC 45-85% Steroid dosage of >10mg of prednisone for at least 6 months Exclusion Criteria: 1. Inability to obtain consent 2. Age less than 18 years of age 3. Female participants of childbearing potential not willing use one of the following methods of birth control for the duration of the study and 90 days after study completion: condoms, sponge, foams, jellies, diaphragm, or non-hormonal intrauterine device, a vasectomized sole partner or abstinence. Females of childbearing potential must have a negative urine pregnancy test at screening visit 4. FVC predicted value is < 45%. 5. Creatine clearance of <30%. 6. History of idiopathic Lactate ≥ 2.2 mmol/L or acidosis on study baseline metabolic profile 7. End-stage fibrotic pulmonary disease 8. Significant underlying liver disease 9. Allergy or intolerance to metformin 10. Allergy or intolerance to albuterol 11. Poor venous access for obtaining blood samples 12. Significant disorder, other than sarcoidosis, that would complicate the treatment evaluation, such as respiratory, cardiac, renal, neurologic, musculoskeletal or seizure disorders. 13. Use of an investigational drug within 30 days prior to screening or within 5 half-lives of the agent, whichever is longer. 14. Currently receiving >40mg prednisone. 15. ALT or AST ≥5 times upper limit of normal (ULN). 16. Leukopenia, as defined by WBC <3.0 cells/mm3 or absolute neutrophil count <1000 mm3 17. Breast feeding. 18. If patient is on immunomodulators, they must be on regimen for ≥3-month period and on a stable dose for ≥ 4 weeks. 19. Most recent nuclear medicine scan or echocardiogram (if done), demonstrating cardiac ejection fraction <35% 20. Participant has persistent or active infections requiring hospitalization or treatment with antibiotics, antiretrovirals, or antifungals within 30 days of baseline. Minocycline and doxycycline are not considered antibiotics when used to treat sarcoidosis. 21. Any significant finding in the patient's medical history or physical or psychiatric exam prior to or after randomization that, in the opinion of the investigator, would affect patient safety or compliance or ability to deliver the study drug according to protocol. 22. On medications that, in the opinion of the investigator, would affect patient safety when taken with metformin 23. History of or receiving treatment for pulmonary hypertension. Receiving biologic medication within the 6 months prior to screening visit.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Active Comparator

    Placebo Comparator

    Arm Label

    Active

    Placebo

    Arm Description

    Patients randomized to metformin will be assigned the active arm.

    Patients randomized to cellulose will be assigned the placebo arm.

    Outcomes

    Primary Outcome Measures

    To assess the steroid-sparing efficacy and safety of oral metformin therapy in patients with progressive pulmonary sarcoidosis.
    Mean daily oral corticosteroid dose post protocol-driven steroid taper at 24-weeks after randomization.

    Secondary Outcome Measures

    To compare cumulative total steroid use between those randomized to metformin or placebo
    • Average dose and cumulative total steroid use in the 24-week study horizon.

    Full Information

    First Posted
    June 6, 2023
    Last Updated
    June 6, 2023
    Sponsor
    University of Maryland, Baltimore
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05910554
    Brief Title
    Investigation of the Efficacy of Metformin Therapy on Pulmonary Sarcoidosis
    Acronym
    MetforminTOP
    Official Title
    Investigation of the Efficacy of Metformin Therapy on Pulmonary Sarcoidosis Phase II Randomized, Double-blind, Placebo-controlled Trial
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    June 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    August 1, 2023 (Anticipated)
    Primary Completion Date
    August 1, 2024 (Anticipated)
    Study Completion Date
    September 1, 2024 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    University of Maryland, Baltimore

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    This is a double blinded, randomized, placebo controlled clinical trial of 40 participants with pulmonary sarcoidosis. Primary Objective: To assess the steroid-sparing efficacy and safety of oral metformin therapy in participants with confirmed progressive pulmonary sarcoidosis for participants with steroid dependent disease.
    Detailed Description
    The purpose of this study is to assess the efficacy of Metformin therapy in terms of steroid-sparing efficacy for sarcoidosis patients with steroid-dependent disease. Given that the morbidity and mortality has proven to be significant in patients with sarcoidosis, we believe there is unprecedented opportunity for improved clinical outcomes if the right interventional agent can be identified. In choosing steroid-sparing effect as the primary outcome, we will be able to detect changes in clinical outcomes that are important to patients and to the scientific community. We anticipate that these improvements will reduce or resolve the necessity of immunosuppressant therapy in these participants. At least 40 participants will be randomized in equal proportion to metformin or placebo. Twenty completed participants per arm provide 80% power to reject (one-sided type I error of 5%) the null hypothesis that mean daily steroid use in the placebo treated group is less than in the metformin treated group using analysis of covariance adjusting for baseline average steroid use.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Sarcoidosis, Pulmonary

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Single Group Assignment
    Masking
    ParticipantCare ProviderInvestigatorOutcomes Assessor
    Masking Description
    Metformin capsules will be encapsulated by the Investigational Drug Services to blind study participants and providers, as well study personnel.
    Allocation
    Randomized
    Enrollment
    40 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Active
    Arm Type
    Active Comparator
    Arm Description
    Patients randomized to metformin will be assigned the active arm.
    Arm Title
    Placebo
    Arm Type
    Placebo Comparator
    Arm Description
    Patients randomized to cellulose will be assigned the placebo arm.
    Intervention Type
    Drug
    Intervention Name(s)
    Metformin
    Other Intervention Name(s)
    glyburide
    Intervention Description
    Patients randomized to metformin will be assigned the active arm.
    Intervention Type
    Drug
    Intervention Name(s)
    Cellulose
    Other Intervention Name(s)
    cellulose powder
    Intervention Description
    Patients randomized to cellulose will be assigned the placebo arm.
    Primary Outcome Measure Information:
    Title
    To assess the steroid-sparing efficacy and safety of oral metformin therapy in patients with progressive pulmonary sarcoidosis.
    Description
    Mean daily oral corticosteroid dose post protocol-driven steroid taper at 24-weeks after randomization.
    Time Frame
    24 weeks
    Secondary Outcome Measure Information:
    Title
    To compare cumulative total steroid use between those randomized to metformin or placebo
    Description
    • Average dose and cumulative total steroid use in the 24-week study horizon.
    Time Frame
    24 weeks

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    85 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Patients with sarcoidosis as defined by the ATS/ERS/WASOG statement on sarcoidosis as defined by the clinical presentation consistent with sarcoidosis, as well as biopsy demonstrating granulomas, and no alternative for the cause of the granulomas, such as tuberculosis for at least one year prior to randomization. Tuberculosis must be ruled out by negative histology and culture. Patients must be symptomatic of pulmonary sarcoidosis with FVC 45-85% Steroid dosage of >10mg of prednisone for at least 6 months Exclusion Criteria: 1. Inability to obtain consent 2. Age less than 18 years of age 3. Female participants of childbearing potential not willing use one of the following methods of birth control for the duration of the study and 90 days after study completion: condoms, sponge, foams, jellies, diaphragm, or non-hormonal intrauterine device, a vasectomized sole partner or abstinence. Females of childbearing potential must have a negative urine pregnancy test at screening visit 4. FVC predicted value is < 45%. 5. Creatine clearance of <30%. 6. History of idiopathic Lactate ≥ 2.2 mmol/L or acidosis on study baseline metabolic profile 7. End-stage fibrotic pulmonary disease 8. Significant underlying liver disease 9. Allergy or intolerance to metformin 10. Allergy or intolerance to albuterol 11. Poor venous access for obtaining blood samples 12. Significant disorder, other than sarcoidosis, that would complicate the treatment evaluation, such as respiratory, cardiac, renal, neurologic, musculoskeletal or seizure disorders. 13. Use of an investigational drug within 30 days prior to screening or within 5 half-lives of the agent, whichever is longer. 14. Currently receiving >40mg prednisone. 15. ALT or AST ≥5 times upper limit of normal (ULN). 16. Leukopenia, as defined by WBC <3.0 cells/mm3 or absolute neutrophil count <1000 mm3 17. Breast feeding. 18. If patient is on immunomodulators, they must be on regimen for ≥3-month period and on a stable dose for ≥ 4 weeks. 19. Most recent nuclear medicine scan or echocardiogram (if done), demonstrating cardiac ejection fraction <35% 20. Participant has persistent or active infections requiring hospitalization or treatment with antibiotics, antiretrovirals, or antifungals within 30 days of baseline. Minocycline and doxycycline are not considered antibiotics when used to treat sarcoidosis. 21. Any significant finding in the patient's medical history or physical or psychiatric exam prior to or after randomization that, in the opinion of the investigator, would affect patient safety or compliance or ability to deliver the study drug according to protocol. 22. On medications that, in the opinion of the investigator, would affect patient safety when taken with metformin 23. History of or receiving treatment for pulmonary hypertension. Receiving biologic medication within the 6 months prior to screening visit.

    12. IPD Sharing Statement

    Plan to Share IPD
    No
    IPD Sharing Plan Description
    No HIPAA data will be provided.

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    Investigation of the Efficacy of Metformin Therapy on Pulmonary Sarcoidosis

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