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Trial record 7 of 37 for:    Chest CT Scan | Recruiting, Not yet recruiting, Available Studies | NIH, U.S. Fed

Effects of Semaglutide in HIV-Associated Lipohypertrophy

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ClinicalTrials.gov Identifier: NCT04019197
Recruitment Status : Recruiting
First Posted : July 15, 2019
Last Update Posted : July 15, 2019
Sponsor:
Collaborators:
Medical University of South Carolina
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Allison Eckard, Medical University of South Carolina

Brief Summary:
This is a randomized, double-blinded, placebo-controlled trial designed to assess the effect of the GLP-1 receptor agonist, semaglutide, on visceral and ectopic fat, insulin resistance, inflammation markers, and the downstream effect of cardiovascular risk in people with HIV. A similarly-designed study will enroll overweight/obese participants without HIV who will match the participants with HIV by gender, age, and BMI, and will run in parallel to the HIV study. The primary endpoints will be visceral and ectopic fat changes over the study period. The secondary endpoints will include changes in markers of inflammation, immune activation, gut integrity, and cardiovascular disease risk assessment.

Condition or disease Intervention/treatment Phase
HIV/AIDS Lipohypertrophy Obesity Drug: Semaglutide Injectable Product Drug: Placebo Phase 2

Detailed Description:
This study is a phase IIb, randomized, double-blinded, placebo-controlled clinical trial of semaglutide in people with HIV-associated lipohypertrophy. Two populations (individuals with HIV and lipohypertrophy and gender-, age-, and BMI-matched HIV-uninfected controls who are overweight/obese) will be studied in separate but similarly-designed studies running in parallel. Participants will be recruited from 2 different sites (Cleveland, OH and Charleston, SC). The duration of the study will be 56 weeks. The interventional phase will last 32 weeks, followed by a 24-week observational phase to assess the sustainability of the intervention. Participants will be randomized 1:1 to receive semaglutide by subcutaneous injection once weekly for 32 weeks (8-week dose escalation phase followed by full-dose for 24 weeks) or matching placebo.The primary objective of this clinical trial is to determine the efficacy of semaglutide in treating lipohypertrophy among non-diabetic people living with HIV by reducing fat accumulation and ectopic fat deposition, altering adipokine levels, improving endothelial function and arterial stiffness, down-regulating key pro-inflammatory cytokines and immune activation without modifying microbial translocation and gut integrity markers. A secondary objective is to determine the difference (if any) in the efficacy of semaglutide in people with HIV compared to an overweight/obese group without HIV.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 208 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effects of GLP-l Receptor Agonists on Cardiometabolic Alterations in HIV-associated Lipohypertrophy
Actual Study Start Date : May 16, 2019
Estimated Primary Completion Date : October 31, 2023
Estimated Study Completion Date : March 31, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS
Drug Information available for: Semaglutide

Arm Intervention/treatment
Experimental: Participants with HIV and lipohypertrophy: semaglutide arm
Participants with HIV/lipohypertrophy will receive semaglutide 0.25 mg x4 weeks, then semaglutide 0.5 mg x4 weeks, then semaglutide 1.0 mg x24 weeks, then no drug x24 weeks.
Drug: Semaglutide Injectable Product
semaglutide subcutaneous injection
Other Names:
  • semaglutide
  • Ozempic

Placebo Comparator: Participants with HIV and lipohypertrophy: placebo arm
Participants with HIV/Lipohypertrophy will receive placebo x32 weeks, then no placebo for 24 weeks.
Drug: Placebo
placebo injection
Other Names:
  • placebo injection
  • placebos

Experimental: Overweight/obese participants without HIV: semaglutide arm
Overweight/obese participants without HIV will receive semaglutide 0.25 mg x4 weeks, then semaglutide 0.5 mg x4 weeks, then semaglutide 1.0 mg x24 weeks, then no drug x24 weeks.
Drug: Semaglutide Injectable Product
semaglutide subcutaneous injection
Other Names:
  • semaglutide
  • Ozempic

Placebo Comparator: Overweight/obese participants without HIV: placebo arm
Overweight/obese participants without HIV will receive placebo x32 weeks, then no placebo for 24 weeks.
Drug: Placebo
placebo injection
Other Names:
  • placebo injection
  • placebos




Primary Outcome Measures :
  1. Changes in visceral abdominal fat [ Time Frame: 56 weeks ]
    A comparison of changes over time will be made between participants with HIV receiving semaglutide vs. placebo in the amount of visceral abdominal fat as measured by abdominal CT scan.

  2. Changes in subcutaneous abdominal fat [ Time Frame: 56 weeks ]
    A comparison of changes over time will be made in the amount of subcutaneous abdominal fat as measured by abdominal CT scan in participants with HIV receiving semaglutide vs. placebo.

  3. Changes in epicardial fat [ Time Frame: 56 weeks ]
    A comparison of changes over time will be made in the amount of epicardial fat as measured by chest CT scan in participants with HIV receiving semaglutide vs. placebo.

  4. Changes in amount of fat by DXA scan [ Time Frame: 56 weeks ]
    A comparison of changes over time will be made between participants with HIV receiving semaglutide vs. placebo in the amount of total fat, limb fat, and trunk fat as measured by whole-body DXA.


Secondary Outcome Measures :
  1. Changes in pulse wave velocity [ Time Frame: 56 weeks ]
    A comparison of changes over time will be made between participants with HIV receiving semaglutide vs. placebo in pulse wave velocity, a measure of arterial stiffness, as a surrogate measure of cardiovascular disease risk.

  2. Changes in EndoPat [ Time Frame: 56 weeks ]
    A comparison of changes over time will be made between participants with HIV receiving semaglutide vs. placebo in EndoPat, a measure of endothelial function, as a surrogate measure of cardiovascular disease risk.

  3. Changes in inflammation [ Time Frame: 56 weeks ]
    A comparison of changes over time will be made between participants with HIV receiving semaglutide vs. placebo in pro-inflammatory markers (sCD14, sCD163, hsCRP, IL-6, sTNFR-1, sTNRF-II) to assess overall level of inflammation.

  4. Changes in gut hormones [ Time Frame: 56 weeks ]
    A comparison of changes over time will be made between participants with HIV receiving semaglutide vs. placebo in the gut hormones, GIP and GLP-1 levels, by means of a mixed-meal tolerance test.

  5. Changes in liver fat [ Time Frame: 56 weeks ]
    A comparison of changes over time will be made between participants with HIV receiving semaglutide vs. placebo in the amount of liver fat, as measured by abdominal CT scan.

  6. Changes in gut integrity [ Time Frame: 56 weeks ]
    A comparison of changes over time will be made between participants with HIV receiving semaglutide vs. placebo in several measures of gut integrity and microbial translocation (I-FABP, zonulin-1, LPS).

  7. Changes in insulin sensitivity [ Time Frame: 56 weeks ]
    A comparison of changes over time will be made between participants with HIV receiving semaglutide vs. placebo in insulin sensitivity by means of assessing HOMA-IR (calculated based on insulin levels and glucose levels).

  8. Changes in glucose metabolism [ Time Frame: 56 weeks ]
    A comparison of changes over time will be made between participants receiving semaglutide vs. placebo in glucose metabolism collectively by assessing oral glucose tolerance, fasting glucose levels, and HgbA1C.

  9. Changes in resting energy expenditure [ Time Frame: 56 weeks ]
    A comparison of changes over time will be made between participants with HIV receiving semaglutide vs. placebo in resting energy expenditure by means of indirect calorimetry.


Other Outcome Measures:
  1. Adipokines and natriuretic peptides [ Time Frame: 56 weeks ]
    A comparison of changes over time will be made between participants with HIV receiving semaglutide vs. placebo in adipokines and natriuretic peptides to help elucidate the potential mechanism by which GLP-1 may affect metabolic endpoints.

  2. Comparison of outcomes for participants with HIV vs. participants without HIV receiving semaglutide [ Time Frame: 56 weeks ]
    All outcome measures will be assessed for differences in changes among participants with HIV receiving semaglutide vs. participants without HIV receiving semaglutide to help determine if GLP-1 receptor agonists work differently in HIV.

  3. Comparison of outcomes for participants with HIV vs. participants without HIV receiving placebo [ Time Frame: 56 weeks ]
    All outcome measures will be assessed for differences in changes over time among participants with HIV receiving placebo vs. participants without HIV receiving placebo to help determine the natural course of lipohypertrophy in HIV vs. obesity in people without HIV.

  4. Changes over time in HIV-associated lipohypertrophy [ Time Frame: 56 weeks ]
    All outcome measures will be assessed for changes over time among participants with HIV receiving placebo to help determine the natural course of lipohypertrophy in HIV.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

To be eligible to participate in this study, INDIVIDUALS WITH HIV must meet all of the following criteria:

  1. Male or female, aged ≥18 years.
  2. HIV-1 infection as documented by any licensed ELISA test kit and confirmed by Western blot at any time prior to study entry. HIV-1 culture, HIV-1 antigen, plasma HIV-1 RNA, or a second antibody test by a method other than ELISA is acceptable as an alternative confirmatory test.
  3. Body mass index ≥25 kg/m2.
  4. Waist circumference and waist-to-hip ratio >95 cm and >0.94 cm, respectively, for men, and >94 cm and >0.88 cm, respectively, for women occurring in the context of HIV treatment.
  5. Subjective evidence of increased abdominal girth occurring after initiation of HIV treatment.
  6. HIV-1 RNA <400 copies/mL for ≥6 months.
  7. Receiving a stable antiretroviral regimen for at least the last 12 weeks prior to study entry with cumulative duration of 1 year of treatment at the time of study entry.
  8. Provision of signed and dated informed consent form and is capable of reading and comprehending the informed consent.
  9. Stated willingness to comply with all study procedures and availability for the duration of the study.
  10. All women of child-bearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to start of study medication. WOCBP is defined as any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy), who is not postmenopausal (defined as amenorrhea 12 consecutive months), or is on hormone replacement therapy (HRT) with documented plasma follicle-stimulating hormone level 35 mIU/mL. Women who are using oral, implanted, or injectable contraceptive hormones or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy or practicing abstinence or where partner is sterile (e.g., vasectomy), should be considered of child-bearing potential.
  11. Female subjects who are not of reproductive potential (have reached menopause or undergone hysterectomy, bilateral oophorectomy or tubal ligation) or whose male partner has undergone successful vasectomy with resulting azoospermia or has azoospermia for any other reason, are eligible without requiring the use of contraception. Patient-reported history of menopause, sterilization, and azoospermia is considered acceptable documentation.
  12. All subjects must not participate in a conception process (e.g. active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization), and if participating in sexual activity that could lead to pregnancy, the female subject/male partner must use condoms (male or female) in addition to one of the following forms of contraception while on study: either a spermicidal agent, diaphragm, cervical cap, IUD, or hormonal-based contraception.
  13. Have no plans to alter antiretroviral therapy, or to undergo any weight loss program, formal exercise training or surgery during the study period, or initiate structured/strategic antiretroviral treatment interruptions.

To be eligible to participate in this study, CONTROLS WITHOUT HIV must meet all of the following criteria:

  1. Male or female, aged ≥18 years.
  2. Documentation of HIV negative test by any FDA-approved HIV testing kit within 30 days prior to study entry.
  3. Waist circumference and waist-to-hip ration >95 cm and >0.94 cm, respectively, for men, and >94 cm and >0.88 cm, respectively, for women.
  4. Body mass index ≥25 kg/m2.
  5. Provision of signed and dated informed consent form and is capable of reading and comprehending the informed consent.
  6. Stated willingness to comply with all study procedures and availability for the duration of the study.
  7. All women of child-bearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to start of study medication. WOCBP is defined as any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy), who is not postmenopausal (defined as amenorrhea 12 consecutive months), or is on hormone replacement therapy (HRT) with documented plasma follicle-stimulating hormone level 35 mIU/mL. Women who are using oral, implanted, or injectable contraceptive hormones or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy or practicing abstinence or where partner is sterile (e.g., vasectomy), should be considered of child-bearing potential.
  8. Female subjects who are not of reproductive potential (have reached menopause or undergone hysterectomy, bilateral oophorectomy or tubal ligation) or whose male partner has undergone successful vasectomy with resulting azoospermia or has azoospermia for any other reason, are eligible without requiring the use of contraception. Patient-reported history of menopause, sterilization, and azoospermia is considered acceptable documentation.
  9. Acceptable documentation of menopause, sterilization, and azoospermia is patient reported history.
  10. All subjects must not participate in a conception process (e.g. active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization), and if participating in sexual activity that could lead to pregnancy, the female subject/male partner must use condoms (male or female) in addition to one of the following forms of contraception while on study: either a spermicidal agent, diaphragm, cervical cap, IUD, or hormonal-based contraception.
  11. Have no plans to undergo any weight loss program, formal exercise training or surgery during the study period.

***Selection of controls will be made so that the group matches the HIV-infected group by age, gender and body mass index***

Exclusion Criteria:

Main exclusion criteria (FOR BOTH GROUPS):

  1. Known cardiovascular disease or diagnosed diabetes. If on metformin without a diabetes diagnoses metformin use has to be constant, uninterrupted for 6 months prior to entry.
  2. Any active or chronic uncontrolled inflammatory condition, infection or cancer.
  3. Women who are pregnant or breastfeeding.
  4. Women with a positive pregnancy test on enrollment or prior to study drug administration.
  5. A clinically-relevant illness within 14 days prior to study entry not explicitly excluded by the protocol, a physical or psychiatric disability, or a laboratory abnormality that might place the subject at increased risk by being exposed to the medications in this study or which might confound the interpretation of this investigation.
  6. Active gastrointestinal symptom Grade >1 within the last month.
  7. Regular use of immunomodulators/agents which could impact inflammation. Regular use of NSAIDS allowed if constant, uninterrupted for 6 months and no plans to alter. Statin use must also be constant, uninterrupted for 6 months prior to study entry. Thyroid medication allowed unless diagnosed with uncontrolled thyroid disease.
  8. Inability to communicate effectively with study personnel.
  9. Use of megestrol acetate, testosterone, or any steroid use beyond normal amounts found in the body within 6 months of study, or intend to start.
  10. Glomerular filtration rate <50 cc/min/1.73 m2.
  11. Hemoglobin <10 g/dL.
  12. Elevated lipase level >1.5 upper limit of normal
  13. AST AND ALT >2.5x upper limit of normal.
  14. Use of growth hormone or growth hormone-releasing hormone in the last year, or intent to start.
  15. History of excessive alcohol use (on average 2 or more drinks a day) , pancreatitis, thyroid cancer, or a diagnosis of multiple endocrine neoplasia (MEN) syndrome type 2.
  16. History of gallbladder or bile duct disease or cholelithiasis.
  17. History of lactose intolerance or inability to consume milk products will be exclusionary for participation in the mixed-meal tolerance test portion of the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04019197


Contacts
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Contact: Grace A McComsey, MD 216-844-5936 grace.mccomsey@uhhospitals.org
Contact: Allison R Eckard, MD 843-876-4541 eckarda@musc.edu

Locations
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United States, Ohio
Case Western Reserve University Recruiting
Cleveland, Ohio, United States, 44106
Contact: Grace A McComsey, MD    216-844-5936    grace.mccomsey@uhhospitals.org   
Contact: Danielle Labbato, RN    216-844-2739    danielle.labbato@uhhospitals.org   
United States, South Carolina
Medical University of South Carolina Not yet recruiting
Charleston, South Carolina, United States, 29425
Contact: Allison R Eckard, MD    843-876-4541    eckarda@musc.edu   
Contact: Lisa Martin, RN    216-844-5936    martinl@musc.edu   
Sponsors and Collaborators
Case Western Reserve University
Medical University of South Carolina
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
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Principal Investigator: Grace A McComsey, MD Case Western Reserve University
Principal Investigator: Allison R Eckard, MD Medical University of South Carolina

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Responsible Party: Allison Eckard, Multiple Principal Investigator, Medical University of South Carolina
ClinicalTrials.gov Identifier: NCT04019197     History of Changes
Other Study ID Numbers: STUDY20190121
R01DK121619 ( U.S. NIH Grant/Contract )
First Posted: July 15, 2019    Key Record Dates
Last Update Posted: July 15, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Sharing of data generated by this project is an essential part of our proposed activities and will be carried out to comply with the NIH policy on Sharing Research Data. We wish to make our results available both to the community of scientists interested in HIV infection, immune activation and co-morbidities, as well as to people living with HIV infection. The data generated in this project will be presented at local, national and international conferences and published in peer-reviewed journals in a timely fashion. All final peer-reviewed manuscripts that arise from this project will be submitted to PubMed Central. The PI will work to facilitate any request made for data produced under this proposal upon publication of data, using standard, university-approved material/data transfer agreements.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
Time Frame: after publication
Access Criteria: individual requests will be reviewed by study PIs.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Allison Eckard, Medical University of South Carolina:
HIV
lipohypertrophy
semaglutide
GLP-1 receptor agonist
obesity
Additional relevant MeSH terms:
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Obesity
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms