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出境医 / 临床实验 / Semaglutide Treatment On Coronary Progression (STOP)

Semaglutide Treatment On Coronary Progression (STOP)

Study Description
Brief Summary:
The purpose of this research study is to see the effect of the diabetes medicine Semaglutide on a condition called atherosclerosis. Atherosclerosis is a narrowing, blockage, or hardening of the arteries due to a build up of calcium. This study will look specifically at the arteries involving the heart.

Condition or disease Intervention/treatment Phase
Type 2 Diabetes Coronary Artery Disease Drug: Semaglutide 2 MG/1.5 ML Subcutaneous Solution Drug: Placebo Phase 4

Detailed Description:
To determine the effects of semaglutide therapy on the morphology and composition of non-calcified coronary atherosclerotic plaque (NCP), including the progression of plaque volume.
Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 140 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Double Blind Placebo Controlled
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effect of Semaglutide on Coronary Atherosclerosis Plaque Progression in Type 2 Diabetics
Actual Study Start Date : April 30, 2019
Estimated Primary Completion Date : June 2021
Estimated Study Completion Date : June 2022
Arms and Interventions
Arm Intervention/treatment
Active Comparator: Semaglutide
Semaglutide 2mg/1.5 ml (1.34 mg/ml) Prefilled pen for SQ injection
Drug: Semaglutide 2 MG/1.5 ML Subcutaneous Solution
Semaglutide 2 MG/1.5 ML Subcutaneous Solution

Placebo Comparator: Placebo
Placebo 1.5 ml, pen-injector for SC injection.
Drug: Placebo
Placebo 1.5 ml, pen-injector for SC injection.

Outcome Measures
Primary Outcome Measures :
  1. Rate of change in non-calcified plaque volume [ Time Frame: 12 months ]
    Rate of change in non-calcified plaque volume


Secondary Outcome Measures :
  1. Rate of change in total plaque volume [ Time Frame: 12 months ]
    Rate of change in total plaque volume


Eligibility Criteria
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Ages Eligible for Study:   40 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Men or women with type 2 diabetes with a glycated hemoglobin level of 7.0% or more, drug naïve, or treated with oral agents and/or basal insulin. For patients on basal insulin at entry, the PI will consider dose reduction of basal insulin according to A1c and risk for hypoglycemia. Patients on SGLT-2 inhibitors may be screened but the agents must be discontinued at least 30 days prior to randomization.
  • Age > 40 years of age at the time of the initial Screening visit (V1) with a diagnosis of T2DM in accordance with American Diabetes Association (ADA) guidelines and with at least one cardiovascular risk factor (hypertension, high cholesterol, family history of premature heart disease or past/current smoking) or prior ASCVD (prior stroke, TIA, claudication, coronary artery disease)
  • Willingness to participate in the study and ability to sign informed consent
  • In the investigator's opinion subjects are willing and likely able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures whether or not they receive investigational product for the duration of the trial.

Exclusion Criteria:

  • History of type 1 diabetes mellitus or a history of ketoacidosis.
  • Current use of GLP-1-receptor agonists or use of a GLP-1 receptor agonist within 3 mos. of screening.
  • Current Use of SGLT-2 inhibitors within 30 days of screening
  • Subjects on prandial insulin or using an insulin pump or pramlintide.
  • Any clinically significant malabsorption condition.
  • History of one or more severe hypoglycemic episodes within 6 months of Screening (V1) or a severe hypoglycemic episode occurring during the interval between the Screening visit (V1) and randomization.
  • Subjects experiencing a cardiovascular event (e.g., myocardial infarction or stroke) or undergoing coronary angioplasty or peripheral intervention procedure between the Screening visit (V1) and randomization.
  • Recent ASCVD Event (stroke, heart attack, ACS or revascularization) within 3 months (90 days) of the screening visit (VI).
  • Subjects undergoing any cardiovascular surgery (e.g., valvular surgery) within 3 months (90 days) of the Screening visit (V1).
  • Subjects with any planned coronary revascularization or peripheral intervention procedure or other cardiovascular surgery.
  • Subjects with New York Heart Association (NYHA) Class III or IV heart failure at the Screening visit (V1).
  • Renal insufficiency (calculated creatinine clearance of <50 ml per minute, MDRD equation).
  • AST or ALT >2 X the upper limit of normal (ULN) at the Screening visit (V1), or a total bilirubin >1.5 X the ULN unless the subject has a history of Gilbert's.
  • Weight in excess of 325 pounds
  • Resting hypotension (systolic blood pressure of <90mmHg) or resting hypertension (systolic blood pressure of >170mmHg or diastolic blood pressure of >110 mmHg) or the treating physician is allowed to adjust background blood pressure medication(s) to lower blood pressure values in order for the subject to be re-assessed for enrollment eligibility.
  • Subject has a history of malignancy ≤5 years prior to signing informed consent, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer.

Note (1) A subject with a history of malignancy >5 years prior to signing informed consent should have no evidence of residual or recurrent disease.

Note (2) a subject with any history of melanoma, leukemia, lymphoma, or renal cell carcinoma is excluded.

  • At randomization, subject has developed a new medical condition, suffered a change in status of an established medical condition, developed a laboratory or ECG abnormality, or required a new treatment or medication during the pre-randomization period which meets any previously described trial exclusion criterion or which, in the opinion of the investigator, exposes the subject to risk by enrolling in the trial.
  • Other severe acute or chronic medical or psychiatric condition or laboratory abnormality at the Screening visit (V1) that may increase the risk associated with trial participation or investigational product administration or may interfere with the interpretation of trial results and, in the judgment of the investigator, would make the subject inappropriate for entry into this trial.
  • Subjects with known allergy to iodinated contrast material
  • Subject is pregnant or breast-feeding, or is expecting to conceive during the trial, including 35 days following the last dose of blinded investigational product.
  • Females of childbearing potential must use adequate contraceptive methods.
  • Participation in other studies involving investigational drug (s) (Phases 1-4) within 30 days before the Screening visit (V1) and/or during trial participation.
  • Family or personal history of multiple endocrine neoplasia type 2 (MEN2) or familial medullary thyroid carcinoma (FMTC)
  • Personal history of non-familial medullary thyroid carcinoma.
  • Known or suspected hypersensitivity to trial products.
Contacts and Locations

Contacts
Layout table for location contacts
Contact: Sajad Hamal, MS 3109749334 ext 7217 shamal@lundquist.org

Locations
Layout table for location information
United States, California
Lundquist Institute for Biomedical Innovation at Harbor UCLA Medical Center Recruiting
Torrance, California, United States, 90502
Contact: Sajad Hamal, MS    310-974-9334 ext 7217    shamal@lundquist.org   
Sponsors and Collaborators
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Investigators
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Principal Investigator: Matthew Budoff, MD Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Tracking Information
First Submitted Date  ICMJE June 10, 2019
First Posted Date  ICMJE June 13, 2019
Last Update Posted Date January 28, 2021
Actual Study Start Date  ICMJE April 30, 2019
Estimated Primary Completion Date June 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 12, 2019)
Rate of change in non-calcified plaque volume [ Time Frame: 12 months ]
Rate of change in non-calcified plaque volume
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 13, 2019)
Rate of change in total plaque volume [ Time Frame: 12 months ]
Rate of change in total plaque volume
Original Secondary Outcome Measures  ICMJE
 (submitted: June 12, 2019)
To assess quantitative changes in total plaque in patients with type 2 diabetes who are on a standard of care regimen receiving once-weekly semaglutide or placebo with CTA [ Time Frame: 12 months ]
Rate of change in total plaque volume with active and placebo compounds
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Semaglutide Treatment On Coronary Progression
Official Title  ICMJE Effect of Semaglutide on Coronary Atherosclerosis Plaque Progression in Type 2 Diabetics
Brief Summary The purpose of this research study is to see the effect of the diabetes medicine Semaglutide on a condition called atherosclerosis. Atherosclerosis is a narrowing, blockage, or hardening of the arteries due to a build up of calcium. This study will look specifically at the arteries involving the heart.
Detailed Description To determine the effects of semaglutide therapy on the morphology and composition of non-calcified coronary atherosclerotic plaque (NCP), including the progression of plaque volume.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Double Blind Placebo Controlled
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Type 2 Diabetes
  • Coronary Artery Disease
Intervention  ICMJE
  • Drug: Semaglutide 2 MG/1.5 ML Subcutaneous Solution
    Semaglutide 2 MG/1.5 ML Subcutaneous Solution
  • Drug: Placebo
    Placebo 1.5 ml, pen-injector for SC injection.
Study Arms  ICMJE
  • Active Comparator: Semaglutide
    Semaglutide 2mg/1.5 ml (1.34 mg/ml) Prefilled pen for SQ injection
    Intervention: Drug: Semaglutide 2 MG/1.5 ML Subcutaneous Solution
  • Placebo Comparator: Placebo
    Placebo 1.5 ml, pen-injector for SC injection.
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 12, 2019)
140
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2022
Estimated Primary Completion Date June 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Men or women with type 2 diabetes with a glycated hemoglobin level of 7.0% or more, drug naïve, or treated with oral agents and/or basal insulin. For patients on basal insulin at entry, the PI will consider dose reduction of basal insulin according to A1c and risk for hypoglycemia. Patients on SGLT-2 inhibitors may be screened but the agents must be discontinued at least 30 days prior to randomization.
  • Age > 40 years of age at the time of the initial Screening visit (V1) with a diagnosis of T2DM in accordance with American Diabetes Association (ADA) guidelines and with at least one cardiovascular risk factor (hypertension, high cholesterol, family history of premature heart disease or past/current smoking) or prior ASCVD (prior stroke, TIA, claudication, coronary artery disease)
  • Willingness to participate in the study and ability to sign informed consent
  • In the investigator's opinion subjects are willing and likely able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures whether or not they receive investigational product for the duration of the trial.

Exclusion Criteria:

  • History of type 1 diabetes mellitus or a history of ketoacidosis.
  • Current use of GLP-1-receptor agonists or use of a GLP-1 receptor agonist within 3 mos. of screening.
  • Current Use of SGLT-2 inhibitors within 30 days of screening
  • Subjects on prandial insulin or using an insulin pump or pramlintide.
  • Any clinically significant malabsorption condition.
  • History of one or more severe hypoglycemic episodes within 6 months of Screening (V1) or a severe hypoglycemic episode occurring during the interval between the Screening visit (V1) and randomization.
  • Subjects experiencing a cardiovascular event (e.g., myocardial infarction or stroke) or undergoing coronary angioplasty or peripheral intervention procedure between the Screening visit (V1) and randomization.
  • Recent ASCVD Event (stroke, heart attack, ACS or revascularization) within 3 months (90 days) of the screening visit (VI).
  • Subjects undergoing any cardiovascular surgery (e.g., valvular surgery) within 3 months (90 days) of the Screening visit (V1).
  • Subjects with any planned coronary revascularization or peripheral intervention procedure or other cardiovascular surgery.
  • Subjects with New York Heart Association (NYHA) Class III or IV heart failure at the Screening visit (V1).
  • Renal insufficiency (calculated creatinine clearance of <50 ml per minute, MDRD equation).
  • AST or ALT >2 X the upper limit of normal (ULN) at the Screening visit (V1), or a total bilirubin >1.5 X the ULN unless the subject has a history of Gilbert's.
  • Weight in excess of 325 pounds
  • Resting hypotension (systolic blood pressure of <90mmHg) or resting hypertension (systolic blood pressure of >170mmHg or diastolic blood pressure of >110 mmHg) or the treating physician is allowed to adjust background blood pressure medication(s) to lower blood pressure values in order for the subject to be re-assessed for enrollment eligibility.
  • Subject has a history of malignancy ≤5 years prior to signing informed consent, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer.

Note (1) A subject with a history of malignancy >5 years prior to signing informed consent should have no evidence of residual or recurrent disease.

Note (2) a subject with any history of melanoma, leukemia, lymphoma, or renal cell carcinoma is excluded.

  • At randomization, subject has developed a new medical condition, suffered a change in status of an established medical condition, developed a laboratory or ECG abnormality, or required a new treatment or medication during the pre-randomization period which meets any previously described trial exclusion criterion or which, in the opinion of the investigator, exposes the subject to risk by enrolling in the trial.
  • Other severe acute or chronic medical or psychiatric condition or laboratory abnormality at the Screening visit (V1) that may increase the risk associated with trial participation or investigational product administration or may interfere with the interpretation of trial results and, in the judgment of the investigator, would make the subject inappropriate for entry into this trial.
  • Subjects with known allergy to iodinated contrast material
  • Subject is pregnant or breast-feeding, or is expecting to conceive during the trial, including 35 days following the last dose of blinded investigational product.
  • Females of childbearing potential must use adequate contraceptive methods.
  • Participation in other studies involving investigational drug (s) (Phases 1-4) within 30 days before the Screening visit (V1) and/or during trial participation.
  • Family or personal history of multiple endocrine neoplasia type 2 (MEN2) or familial medullary thyroid carcinoma (FMTC)
  • Personal history of non-familial medullary thyroid carcinoma.
  • Known or suspected hypersensitivity to trial products.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 40 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Sajad Hamal, MS 3109749334 ext 7217 shamal@lundquist.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03985384
Other Study ID Numbers  ICMJE 22174-01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Matthew J. Budoff, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Study Sponsor  ICMJE Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Matthew Budoff, MD Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
PRS Account Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Verification Date January 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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