Role of Insulin Action in Psoriasis Pathogenesis

Launched by COLUMBIA UNIVERSITY · Jan 29, 2024

Keywords

ClinConnect Summary

This clinical trial is focused on understanding the role of insulin in people with plaque psoriasis, a common skin condition characterized by red, scaly patches. Researchers want to find out if insulin action in the skin is different from its action elsewhere in the body, especially since many people with psoriasis also have insulin resistance, a condition where the body doesn’t respond well to insulin. Participants will undergo a skin biopsy, which is a small sample taken from both affected and unaffected areas of skin after fasting overnight. This will help scientists study how insulin behaves in those specific skin areas.

To be eligible for this study, participants should be between 18 and 75 years old, have a body mass index (BMI) between 25 and 40 (indicating they are overweight or obese), and have a diagnosis of plaque psoriasis. They must be able to give informed consent in English or Spanish. Participants will receive more information about the study before agreeing to take part, and they will be monitored closely throughout the trial. Importantly, anyone currently using diabetes medications or with certain medical conditions related to diabetes will not be eligible. Overall, this trial aims to shed light on how insulin may impact skin health in individuals with psoriasis.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. Body mass index of 25.0-40.0 kg/m2
• • 2. Able to understand written and spoken English and/or Spanish
• • 3. Written informed consent (in English or Spanish) and any locally required authorization (e.g., Health Insurance Portability and Accountability Act) obtained from the participant prior to performing any protocol-related procedures, including screening evaluations.
• • 4. Diagnosed with plaque psoriasis, documented using Psoriasis Area and Severity Index (PASI)
• 5. Glucose metabolism status as follows (determined only retrospectively based on data collected during the study):
• * For Insulin Sensitive (IS) group:
• • Hemoglobin A1c \< 5.7%, and
• • Fasting plasma glucose \< 95 mg/dL, and
• • Fasting plasma insulin \< 10 μIU/mL
• * For Insulin Intermediate (II) group:
• • Hemoglobin A1c \< 6.5%, and
• • Fasting plasma glucose 80-125 mg/dL, and
• • Fasting plasma insulin 10-14 μIU/mL
• * For Insulin Resistant (IR) group:
• • Hemoglobin A1c \< 6.5%, and
• • Fasting plasma glucose 80-125 mg/dL, and
• • Fasting plasma insulin ≥ 15 μIU/mL
• Exclusion Criteria:
• • 1. Inability to provide informed consent in English or Spanish
• 2. Concerns arising at screening visit (any of the following):
• 3. Laboratory evidence of diabetes mellitus, either determined during the study or based on previous documentation:
• • Hemoglobin A1c ≥ 6.5%, and/or
• • Fasting plasma glucose ≥ 126 mg/dL
• • Plasma glucose ≥ 200 mg/dL at 2 hours after ingestion of a 75-g oral glucose load
• • Random plasma glucose ≥ 200 mg/dL associated with typical hyperglycemic symptoms, diabetic ketoacidosis, or hyperglycemic-hyperosmolar state
• • 4. History of gestational diabetes mellitus
• 5. Use of antidiabetic medications within the 90 days prior to screening, including those prescribed for other indications (e.g., weight control, restoration of ovulation in of polycystic ovarian syndrome), including:
• • • Metformin, thiazolidinediones, sulfonylureas, meglitinides, dipeptidyl peptidase-4 (DPP4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, sodium/glucose cotransporter 2 (SGLT2) inhibitors, amylin mimetics, acarbose, insulin
• • 6. Clinical concern for absolute insulin deficiency (e.g., type 1 diabetes, pancreatic disease)
• • 7. Reproductive concerns
• i. Women of childbearing potential not using highly effective contraception, defined as:
• • Surgical sterilization (e.g., bilateral tubal occlusion, bilateral oophorectomy and/or salpingectomy, hysterectomy)
• • Combined oral contraceptive pills taken daily, including during the study
• • Intrauterine device (levonorgestrel-eluting or copper) active at the time of the study
• • Medroxyprogesterone acetate (Depo-Provera®) injection active at the time of the study
• • Etonogestrel implants (e.g., Implanon®, etc.) active at the time of the study
• • Norelgestromin/ethinyl estradiol transdermal system (e.g., Ortho-Evra®) active at the time of the study
• • ii. Women currently pregnant
• • iii. Women currently breastfeeding
• 8. Known, documented history, at the time of screening, of any of the following medical conditions:
• • i. Bleeding disorders, including due to anticoagulation or use of P2Y12 inhibitors ii. Anemia requiring treatment iii. Glucose-6-phosphate dehydrogenase (G6PD) deficiency
• 9. Use of medications associated methemoglobinemia within 48 hours of shave biopsy procedures:
• • i. Nitrates/nitrites: nitric oxide, nitroglycerin, nitroprusside, nitrous oxide ii. Antineoplastics: cyclophosphamide, flutamide, hydroxyurea, ifosfamide, rasburicase iii. Antibiotics: dapsone, nitrofurantoin, paraaminosalicylic acid, sulfonamides iv. Antimalarials: chloroquine, primaquine v. Anticonvulsants: phenobarbital, phenytoin, valproic acid vi. Others: acetaminophen, metoclopramide, quinine, sulfasalazine
• • 10. History of severe infection or ongoing febrile illness within 30 days of screening
• • 11. Any other disease, condition, or laboratory value that, in the opinion of the investigator, would place the participant at an unacceptable risk and/or interfere with the analysis of study data.
• • 12. Known allergy/hypersensitivity to any component of the medicinal product formulations (including amide anesthetics), IV infusion equipment, plastics, adhesive or silicone, history of infusion site reactions with IV administration of other medicines, or ongoing clinically important allergy/hypersensitivity as judged by the investigator.
• • 13. Concurrent enrollment in another clinical study of any investigational drug therapy within 6 months prior to screening or within 5 half-lives of an investigational agent, whichever is longer.