Role of Insulin Action in Psoriasis Pathogenesis

NCT06242847 | Terminated

• 1 other identifier: AAAU4674
• Study Type: observational
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this study is to collect more information from people with plaque psoriasis and to determine if insulin plays a role in the pathogenesis of psoriasis. The main question it aims to answer is if insulin action is preserved or even enhanced in psoriatic lesions despite insulin resistance elsewhere. Participants with plaque psoriasis will have punch biopsies taken of lesional and non-lesional skin after an overnight fast and then during an oral glucose tolerance test. Biopsy specimens will then be assessed for markers of insulin action.

Conditions

Insulin Resistance; PreDiabetes; Overweight and Obesity; Psoriasis; Plaque Psoriasis

Keywords

Insulin; Insulin resistance; Psoriasis

Outcome Measures

Primary Outcomes (1)

• Skin insulin sensitivity: ratio of phosphorylated to total AKT in skin biopsies

  Investigators will perform Western blots on skin biopsies using antibodies to phosphorylated (T308, S473) and total AKT. The ratio of phosphorylated to total AKT will be determined using densitometry of Western blots and/or by enzyme-linked immunosorbent assays (ELISA), each measured in arbitrary units (AU).

  Up to 120 minutes from the start of OGTT

Secondary Outcomes (5)

• Serum triglyceride (TG) level during OGTT

  During OGTT (up to 120 minutes from start of OGTT)

• Serum free fatty acid (FFA) levels during OGTT

  During OGTT (up to 120 minutes from start of OGTT)

• Fasting plasma glucose level

  Before OGTT (baseline = 0 minutes), During OGTT (up to 120 minutes from start of OGTT)

• Fasting serum insulin level

  Before OGTT (baseline = 0 minutes), During OGTT (up to 120 minutes from start of OGTT)

• Fasting serum C-peptide level

  Before OGTT (baseline = 0 minutes), During OGTT (up to 120 minutes from start of OGTT)

Study Arms (3)

Insulin Sensitive (IS) with psoriasis

Patients with plaque psoriasis found to have: * Hemoglobin A1c \< 5.7% * Fasting plasma glucose: \< 95 mg/dL * Fasting serum insulin: \< 10 micro-international units per milliliter (μIU/mL) * 2-hour post-challenge glucose \< 140 mg/dL NOTE: Group assignments made retroactively based on the observational study results.

Diagnostic Test: Oral glucose tolerance test (OGTT); Procedure: Skin punch biopsy

Insulin Intermediate (II) with psoriasis

Patients with plaque psoriasis found to have: * Hemoglobin A1c \< 6.5% * Fasting plasma glucose \<125 mg/dL * Fasting serum insulin: \<15 μIU/mL * 2-hour post-challenge glucose \< 200 mg/dL NOTE: Group assignments made retroactively based on the observational study results. • Not otherwise meeting all criteria for inclusion in the IS group

Diagnostic Test: Oral glucose tolerance test (OGTT); Procedure: Skin punch biopsy

Insulin Resistant (IR) with psoriasis

Patients with plaque psoriasis found to have: * Fasting serum/plasma insulin ≥ 15 μIU/mL * Fasting plasma glucose 80-125 mg/dL and * Hemoglobin A1c \< 6.5% and * 2-hour post-challenge glucose \< 200 mg/dL NOTE: Group assignments made retroactively based on the observational study results.

Diagnostic Test: Oral glucose tolerance test (OGTT); Procedure: Skin punch biopsy

Interventions

Oral glucose tolerance test (OGTT) DIAGNOSTIC_TEST

Participants ingest 75 g of glucose in 10 fl oz aqueous solution (fruit flavored) after an overnight fast. Blood is drawn at baseline (t = 0 min) and at 120 min after ingestion. This test is non-experimental.

Insulin Intermediate (II) with psoriasis; Insulin Resistant (IR) with psoriasis; Insulin Sensitive (IS) with psoriasis

Skin punch biopsy PROCEDURE

Punch biopsies are taken from lesional (psoriatic) and non-lesional skin after an overnight fast and at 120 min after ingestion of glucose during OGTT. This procedure is non-experimental.

Insulin Intermediate (II) with psoriasis; Insulin Resistant (IR) with psoriasis; Insulin Sensitive (IS) with psoriasis

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with plaque psoriasis but without diabetes mellitus

You may qualify if:

• Body mass index of 25.0-40.0 kg/m2
• Able to understand written and spoken English and/or Spanish
• 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.
• Diagnosed with plaque psoriasis, documented using Psoriasis Area and Severity Index (PASI)
• 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, and
• hour post-challenge glucose \< 140 mg/dL
• For Insulin Intermediate (II) group:
• Hemoglobin A1c \< 6.5%, and
• Fasting plasma glucose 80-125 mg/dL, and
• Fasting plasma insulin \< 15 μIU/mL, and
• 2-hour post-challenge glucose \< 200 mg/dL, and

You may not qualify if:

• Inability to provide informed consent in English or Spanish
• 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
• History of gestational diabetes mellitus
• 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
• Clinical concern for absolute insulin deficiency (e.g., type 1 diabetes, pancreatic disease)
• 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

Sponsors & Collaborators

• Columbia University: lead

Study Sites (1)

Columbia University Irving Medical Center

New York, New York, 10032, United States

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

* Blood samples during OGTT: fasting and at 120 min after ingestion of 75 g of glucose * Skin punch biopsies of lesional (psoriatic) and non-lesional skin taken while fasting and at 120 min after ingestion of 75 g glucose

MeSH Terms

Conditions

Psoriasis; Insulin Resistance; Prediabetic State; Overweight; Obesity

Interventions

Glucose Tolerance Test

Condition Hierarchy (Ancestors)

Skin Diseases, Papulosquamous; Skin Diseases; Skin and Connective Tissue Diseases; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Diabetes Mellitus; Endocrine System Diseases; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Blood Chemical Analysis; Clinical Chemistry Tests; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Endocrine; Investigative Techniques

Study Officials

• Joshua R Cook, MD, PhD

  Columbia University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: January 29, 2024
• First Posted: February 5, 2024
• Study Start: February 2, 2024
• Primary Completion: November 12, 2025
• Study Completion: November 12, 2025
• Last Updated: February 17, 2026

Record last verified: 2026-02

Locations

US (1)