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| ID | Type | Description | Link |
|---|---|---|---|
| U54GM138062 | U.S. NIH Grant/Contract | View source |
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This is a prospective cohort study of 12 overweight (with one or more weight-related condition) or obese adults with well controlled HIV-1 on antiretroviral therapy (ART). An initial dose of tirzepatide (TZP) 2.5 mg subcutaneous (SQ) once weekly will be given, escalated by 2.5 mg at 4-week intervals to a final dose of 7.5mg. The investigators will collect the following information via review of the medical record: age, race/ethnicity, sex, medical conditions, medications, most recent standard of care HIV labs (including T-cell panel and HIV-1 viral load). The primary outcome will be the change in baseline body weight at 12 weeks. Secondary outcomes will be changes in body composition, liver fat content and liver stiffness, inflammatory markers, cardiometabolic markers (lipids and HbA1c), and monocytes at 12 weeks. There will be a 4-week safety follow up off TZP.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Tirzepatide | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tirzepatide | Drug | Tirzepatide is approved by the Food and Drug Administration (FDA) for the treatment of type 2 diabetes, obesity and overweight with at least one weight-related medical condition, and moderate to severe obstructive sleep apnea. An initial dose of TZP 2.5 mg subcutaneous (SQ) once weekly will be given, escalated by 2.5 mg at 4-week intervals to a final dose of 7.5mg. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Baseline Body Weight | The primary outcome will be the change in baseline body weight (measured in lbs) at 12 weeks. | 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Inflammatory Markers: GM-CSF | All biomarkers will be assayed from banked plasma using a Luminex multiplex assay and ELISAs performed per manufacturer's instructions. A Cytokine 10-Plex Human Panel (ThermoFisher Scientific) with data acquired using Luminex 200TM system (Luminex) and ELISAs (ThermoFisher Scientific) with data acquired using a Victor X3 plate reader (PerkinElmer) will be utilized to measure the following inflammatory biomarkers: GM-CSF. Cytokine standards supplied by the manufacturer will be run in duplicate on each plate. |
| Measure | Description | Time Frame |
|---|---|---|
| Biorepository samples for future research | Obtaining blood specimens for banking in the biorepository for future analyses (frozen for retrospective analysis) related to HIV, cardiometabolic diseases, inflammation and the immune system. Biorespository specimens will be collected at baseline, week 12, week 16 and early discontinuation visits. It will not include genetic testing. The biorepository will enable the development of new hypotheses to further contribute toward understanding of HIV, the immune system, chronic inflammation, and cardiometabolic disease. |
Age ≥ 18 years
HIV-1 infection (well controlled)
Stable ART
· Receiving a stable antiretroviral regimen for at least 1 year prior to study entry
Overweight
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| John A Burns School of Medicine | Honolulu | Hawaii | 96813 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28435757 | Background | Morisako AK, Tauali'i M, Ambrose AJH, Withy K. Beyond the Ability to Pay: The Health Status of Native Hawaiians and Other Pacific Islanders in Relationship to Health Insurance. Hawaii J Med Public Health. 2017 Mar;76(3 Suppl 1):36-41. | |
| 38417572 | Background | Hoagland A, Kipping S. Challenges in Promoting Health Equity and Reducing Disparities in Access Across New and Established Technologies. Can J Cardiol. 2024 Jun;40(6):1154-1167. doi: 10.1016/j.cjca.2024.02.014. Epub 2024 Feb 28. |
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| ID | Term |
|---|---|
| D009765 | Obesity |
| D050177 | Overweight |
| ID | Term |
|---|---|
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
| D001835 | Body Weight |
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| ID | Term |
|---|---|
| D000098860 | Tirzepatide |
| ID | Term |
|---|---|
| D000067757 | Glucagon-Like Peptide-1 Receptor |
| D000067756 | Glucagon-Like Peptide Receptors |
| D043562 | Receptors, G-Protein-Coupled |
| D011956 | Receptors, Cell Surface |
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|
| 12 weeks |
| Change in cardiometabolic markers | We will evaluate HbA1c and a lipid profile at the baseline, week 12 and week 16 study visits. | 12 weeks |
| Monocyte Subset Analysis | Monocyte subsets will be phenotyped from thawed/washed banked cryopreserved PBMCs (from blood drawn at baseline, week 12, and week 16) using a multiparametric panel of conjugated monoclonal antibodies: CD3, CD14, CD16, CD56, CD19, CD20, HLA-DR antibodies with Live/Dead fixable yellow dead cell stain (YARD). Data will be acquired on a 4-laser BD LSRFortessa Flow Cytometer with all compensation and gating analyses performed with the FlowJo analytical software to determine levels of classical (CD14 ++ CD16 -), intermediate (CD14 ++ CD16 +), non-classical (CD14 + CD16 ++), and transitional (CD14 + CD16 -) monocytes. | Week 12 and week 16 |
| Change in Inflammatory Markers: IFN-γ | All biomarkers will be assayed from banked plasma using a Luminex multiplex assay and ELISAs performed per manufacturer's instructions. A Cytokine 10-Plex Human Panel (ThermoFisher Scientific) with data acquired using Luminex 200TM system (Luminex) and ELISAs (ThermoFisher Scientific) with data acquired using a Victor X3 plate reader (PerkinElmer) will be utilized to measure the following inflammatory biomarkers: IFN-γ. Cytokine standards supplied by the manufacturer will be run in duplicate on each plate. | 12 weeks |
| Change in Inflammatory Markers: IL-1β | All biomarkers will be assayed from banked plasma using a Luminex multiplex assay and ELISAs performed per manufacturer's instructions. A Cytokine 10-Plex Human Panel (ThermoFisher Scientific) with data acquired using Luminex 200TM system (Luminex) and ELISAs (ThermoFisher Scientific) with data acquired using a Victor X3 plate reader (PerkinElmer) will be utilized to measure the following inflammatory biomarkers: IL-1β. Cytokine standards supplied by the manufacturer will be run in duplicate on each plate. | 12 weeks |
| Change in Inflammatory Markers: IL-2 | All biomarkers will be assayed from banked plasma using a Luminex multiplex assay and ELISAs performed per manufacturer's instructions. A Cytokine 10-Plex Human Panel (ThermoFisher Scientific) with data acquired using Luminex 200TM system (Luminex) and ELISAs (ThermoFisher Scientific) with data acquired using a Victor X3 plate reader (PerkinElmer) will be utilized to measure the following inflammatory biomarkers: IL-2. Cytokine standards supplied by the manufacturer will be run in duplicate on each plate. | 12 weeks |
| Change in Inflammatory Markers: IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10 | All biomarkers will be assayed from banked plasma using a Luminex multiplex assay and ELISAs performed per manufacturer's instructions. A Cytokine 10-Plex Human Panel (ThermoFisher Scientific) with data acquired using Luminex 200TM system (Luminex) and ELISAs (ThermoFisher Scientific) with data acquired using a Victor X3 plate reader (PerkinElmer) will be utilized to measure the following inflammatory biomarkers: IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10. Cytokine standards supplied by the manufacturer will be run in duplicate on each plate. | 12 weeks |
| Change in Inflammatory Markers: TNF-α | All biomarkers will be assayed from banked plasma using a Luminex multiplex assay and ELISAs performed per manufacturer's instructions. A Cytokine 10-Plex Human Panel (ThermoFisher Scientific) with data acquired using Luminex 200TM system (Luminex) and ELISAs (ThermoFisher Scientific) with data acquired using a Victor X3 plate reader (PerkinElmer) will be utilized to measure the following inflammatory biomarkers: TNF-α. Cytokine standards supplied by the manufacturer will be run in duplicate on each plate. | 12 weeks |
| Change in Inflammatory Markers: NFkB | All biomarkers will be assayed from banked plasma using a Luminex multiplex assay and ELISAs performed per manufacturer's instructions. A Cytokine 10-Plex Human Panel (ThermoFisher Scientific) with data acquired using Luminex 200TM system (Luminex) and ELISAs (ThermoFisher Scientific) with data acquired using a Victor X3 plate reader (PerkinElmer) will be utilized to measure the following inflammatory biomarkers: NFkB. Cytokine standards supplied by the manufacturer will be run in duplicate on each plate. | 12 weeks |
| Change in Inflammatory Markers: sCD163, and sCD14 | All biomarkers will be assayed from banked plasma using a Luminex multiplex assay and ELISAs performed per manufacturer's instructions. A Cytokine 10-Plex Human Panel (ThermoFisher Scientific) with data acquired using Luminex 200TM system (Luminex) and ELISAs (ThermoFisher Scientific) with data acquired using a Victor X3 plate reader (PerkinElmer) will be utilized to measure the following inflammatory biomarkers: sCD163, and sCD14. Cytokine standards supplied by the manufacturer will be run in duplicate on each plate. | 12 weeks |
| Body composition | Body composition (total, peripheral and truncal fat, and lean tissue) by dual energy absorptiometry (DEXA) | 12 weeks |
| Waist circumference | Changes in waist circumference over 12 weeks of therapy | 12 weeks |
| Liver fat content | Changes in Liver fat content (Controlled Attenuation Parameter, CAP) over 12 weeks | 12 weeks |
| Liver stiffness measurement (LSM) | Changes in Liver stiffness measurement (LSM) over 12 weeks | 12 weeks |
| The biorepository samples (only) will be banked for future analysis for separate research (related or unrelated to this project) for up to 7 years post-study completion. |
| 29082920 | Background | Liang H, Xie Z, Shen T. Monocyte activation and cardiovascular disease in HIV infection. Cell Mol Immunol. 2017 Dec;14(12):960-962. doi: 10.1038/cmi.2017.109. Epub 2017 Oct 30. No abstract available. |
| 25590212 | Background | Apovian CM, Aronne LJ, Bessesen DH, McDonnell ME, Murad MH, Pagotto U, Ryan DH, Still CD; Endocrine Society. Pharmacological management of obesity: an endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2015 Feb;100(2):342-62. doi: 10.1210/jc.2014-3415. Epub 2015 Jan 15. |
| 32753461 | Background | Wharton S, Lau DCW, Vallis M, Sharma AM, Biertho L, Campbell-Scherer D, Adamo K, Alberga A, Bell R, Boule N, Boyling E, Brown J, Calam B, Clarke C, Crowshoe L, Divalentino D, Forhan M, Freedhoff Y, Gagner M, Glazer S, Grand C, Green M, Hahn M, Hawa R, Henderson R, Hong D, Hung P, Janssen I, Jacklin K, Johnson-Stoklossa C, Kemp A, Kirk S, Kuk J, Langlois MF, Lear S, McInnes A, Macklin D, Naji L, Manjoo P, Morin MP, Nerenberg K, Patton I, Pedersen S, Pereira L, Piccinini-Vallis H, Poddar M, Poirier P, Prud'homme D, Salas XR, Rueda-Clausen C, Russell-Mayhew S, Shiau J, Sherifali D, Sievenpiper J, Sockalingam S, Taylor V, Toth E, Twells L, Tytus R, Walji S, Walker L, Wicklum S. Obesity in adults: a clinical practice guideline. CMAJ. 2020 Aug 4;192(31):E875-E891. doi: 10.1503/cmaj.191707. No abstract available. |
| 35658024 | Background | Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, Kiyosue A, Zhang S, Liu B, Bunck MC, Stefanski A; SURMOUNT-1 Investigators. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022 Jul 21;387(3):205-216. doi: 10.1056/NEJMoa2206038. Epub 2022 Jun 4. |
| 38501237 | Background | Nguyen Q, Wooten D, Lee D, Moreno M, Promer K, Rajagopal A, Tan M, Tang M, Duren K, Yin J, Hill L. Glucagon-like Peptide 1 Receptor Agonists Promote Weight Loss Among People With HIV. Clin Infect Dis. 2024 Oct 15;79(4):978-982. doi: 10.1093/cid/ciae151. |
| 19072098 | Background | Crum-Cianflone N, Tejidor R, Medina S, Barahona I, Ganesan A. Obesity among patients with HIV: the latest epidemic. AIDS Patient Care STDS. 2008 Dec;22(12):925-30. doi: 10.1089/apc.2008.0082. |
| 34631899 | Background | Lv T, Cao W, Li T. HIV-Related Immune Activation and Inflammation: Current Understanding and Strategies. J Immunol Res. 2021 Sep 29;2021:7316456. doi: 10.1155/2021/7316456. eCollection 2021. |
| 38278941 | Background | Lenharo M. Obesity drugs have another superpower: taming inflammation. Nature. 2024 Feb;626(7998):246. doi: 10.1038/d41586-024-00118-4. No abstract available. |
| 37569635 | Background | Todosenko N, Khaziakhmatova O, Malashchenko V, Yurova K, Bograya M, Beletskaya M, Vulf M, Mikhailova L, Minchenko A, Soroko I, Khlusov I, Litvinova L. Adipocyte- and Monocyte-Mediated Vicious Circle of Inflammation and Obesity (Review of Cellular and Molecular Mechanisms). Int J Mol Sci. 2023 Jul 31;24(15):12259. doi: 10.3390/ijms241512259. |
| 39448830 | Background | Sotak M, Clark M, Suur BE, Borgeson E. Inflammation and resolution in obesity. Nat Rev Endocrinol. 2025 Jan;21(1):45-61. doi: 10.1038/s41574-024-01047-y. Epub 2024 Oct 24. |
| 38466272 | Background | Yanovski SZ, Yanovski JA. Approach to Obesity Treatment in Primary Care: A Review. JAMA Intern Med. 2024 Jul 1;184(7):818-829. doi: 10.1001/jamainternmed.2023.8526. |
| D012816 |
| Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D008565 | Membrane Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D011964 | Receptors, Gastrointestinal Hormone |
| D018000 | Receptors, Peptide |