Graded Insulin Suppression Test P&F

NCT06592261 | Recruiting Phase 1 FDA Drug

• 4 other identifiers: AAAV24813P30DK063608-21K12DK133995K23DK140614
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this study is to learn about how the hormone insulin controls blood sugar in a variety of people. The main question it aims to answer is about how much insulin the body actually needs to maintain a normal blood sugar level. Participants will be asked to come in for a one-day study visit in which they will undergo a "graded insulin suppression test" ("GIST"). The GIST involves intravenous (into the vein) infusions of octreotide, a medication that turns off the body's own production of insulin, as well as replacement of insulin at two different levels (low and high), with or without replacement of glucagon, and glucose (sugar). The study investigators will check blood sugar levels every few minutes during the procedure to determine the effect of the two different insulin levels. This study will evaluate the GIST in both healthy volunteers and those at higher risk for type 2 diabetes.

Conditions

Insulin Resistance; Obesity; Hyperinsulinemia; Healthy

Keywords

Insulin resistance; Hyperinsulinemia; Type 2 diabetes; Obesity

Outcome Measures

Primary Outcomes (2)

• Steady-state plasma glucose at euinsulinemia (E-SSG)

  Plasma glucose level at steady state while insulin infusion rate is 4 mU/m2/min (units: mg/dL)

  150-180 minutes during GIST protocol

• Steady-state plasma glucose at hyperinsulinemia (H-SSG)

  Plasma glucose level at steady state while insulin infusion rate is 32 mU/m2/min and glucose infusion rate is 267 mg/m2/min, reflective of insulin sensitivity (units: mg/dL)

  270-300 minutes during GIST protocol

Secondary Outcomes (2)

• Steady-state plasma free fatty acids (FFA) at euinsulinemia

  150-180 minutes during GIST protocol

• Steady-state plasma free fatty acids (FFA) at hyperinsulinemia

  270-300 minutes during GIST protocol

Other Outcomes (6)

• Steady-state serum insulin at euinsulinemia (E-SSI)

  150-180 minutes during GIST protocol

• Steady-state serum insulin at hyperinsulinemia (H-SSI)

  270-300 minutes during GIST protocol

• Steady-state plasma glucagon level at euinsulinemia

  150-180 minutes during GIST protocol

Study Arms (3)

Reference (healthy control) group

EXPERIMENTAL

Healthy volunteers with body mass index of 18-25 kg/m2, fasting serum insulin \< 10 mU/L, hemoglobin A1c \< 5.7%, and fasting plasma glucose \< 100 mg/dL

Drug: Insulin regular, 2.0-3.2 mU/m2/min (euinsulinemia); Drug: Insulin regular, 32 mU/m2/min (hyperinsulinemia); Drug: Octreotide Acetate, 6-45 ng/kg/min; Drug: Dextrose 20 % in Water; Drug: Glucagon, 0-0.5 ng/kg/min

Euinsulinemic group

EXPERIMENTAL

Volunteers with body mass index of 30-45 kg/m2, fasting serum insulin \< 10 mU/L, hemoglobin A1c \< 5.7%, and fasting plasma glucose \< 100 mg/dL

Drug: Insulin regular, 2.0-3.2 mU/m2/min (euinsulinemia); Drug: Insulin regular, 32 mU/m2/min (hyperinsulinemia); Drug: Octreotide Acetate, 6-45 ng/kg/min; Drug: Dextrose 20 % in Water; Drug: Glucagon, 0-0.5 ng/kg/min

Hyperinsulinemic group

EXPERIMENTAL

Volunteers with body mass index of 30-45 kg/m2, fasting serum insulin \>= 13 mU/L, hemoglobin A1c \< 5.7%, and fasting plasma glucose \< 100 mg/dL

Drug: Insulin regular, 2.0-3.2 mU/m2/min (euinsulinemia); Drug: Insulin regular, 32 mU/m2/min (hyperinsulinemia); Drug: Octreotide Acetate, 6-45 ng/kg/min; Drug: Dextrose 20 % in Water; Drug: Glucagon, 0-0.5 ng/kg/min

Interventions

Insulin regular, 32 mU/m2/min (hyperinsulinemia) DRUG

Insulin infusion to induce hyperinsulinemia for assessment of insulin sensitivity

Euinsulinemic group; Hyperinsulinemic group; Reference (healthy control) group

Octreotide Acetate, 6-45 ng/kg/min DRUG

Suppression of endogenous insulin secretion

Euinsulinemic group; Hyperinsulinemic group; Reference (healthy control) group

Dextrose 20 % in Water DRUG

Production of steady-state plasma glucose (SSPG) reflective of insulin sensitivity at hyperinsulinemia

Euinsulinemic group; Hyperinsulinemic group; Reference (healthy control) group

Glucagon, 0-0.5 ng/kg/min DRUG

Replacement of endogenous glucagon suppressed by octreotide. (Use is optional at the PI's discretion.)

Euinsulinemic group; Hyperinsulinemic group; Reference (healthy control) group

Insulin regular, 2.0-3.2 mU/m2/min (euinsulinemia) DRUG

Insulin infusion to recapitulate euinsulinemia (normal basal insulin)

Euinsulinemic group; Hyperinsulinemic group; Reference (healthy control) group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Body mass index of 18-25 and 30-45 kg/m2
• Able to understand written and spoken English and/or Spanish
• Fasting euinsulinemia (fasting serum insulin of 4-10 μU/mL) for reference group or hyperinsulinemia (fasting serum insulin ≥ 13 μU/mL) for hyperinsulinemic group on screening labs
• 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.

You may not qualify if:

• Unable to provide informed consent in English or Spanish
• Unwillingness to use only bedpan or urinal to void or to refrain from non-emergent mobile device use during the GIST
• Documented weight loss of ≥ 5% of baseline within the previous 6 months
• Systolic blood pressure \< 90 mm Hg or \> 160 mm Hg, and/or
• Diastolic blood pressure \< 60 mm Hg or \> 100 mm Hg
• Abnormal resting heart rate: \< 60 or ≥ 110 bpm
• Sinus brady or tachycardia that has been worked up and considered benign by the recruit's personal physician may be permitted at the PI's discretion
• Abnormal screening electrocardiogram (or if on file, performed within previous 90 d):
• Non-sinus rhythm
• Heart conduction blocks
• Previously unknown ischaemic changes that persist on repeat EKG:
• ST elevations
• T-wave inversions in a vascular distribution
• Hemoglobin A1c ≥ 5.7%, and/or
• Fasting plasma glucose ≥ 100 mg/dL

Sponsors & Collaborators

• Columbia University: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator
• University of Pisa: collaborator

Study Sites (1)

Columbia University Irving Medical Center

New York, New York, 10032, United States

RECRUITING

MeSH Terms

Conditions

Insulin Resistance; Hyperinsulinism; Obesity; Diabetes Mellitus, Type 2

Interventions

Insulin; Octreotide; Glucose; Water; Glucagon

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Diabetes Mellitus; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Proinsulin; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Hexoses; Monosaccharides; Sugars; Carbohydrates; Hydroxides; Alkalies; Inorganic Chemicals; Anions; Ions; Electrolytes; Oxides; Oxygen Compounds; Proglucagon

Study Officials

• Joshua R Cook, MD, PhD

  Columbia University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Joshua R Cook, MD, PhD

CONTACT

2123056289; jrc2175@cumc.columbia.edu

Ishwari Nagnur

CONTACT

2123059336; imn2113@cumc.columbia.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: September 9, 2024
• First Posted: September 19, 2024
• Study Start: September 16, 2024
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: December 9, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Time Frame: Scientific data will be shared as soon as possible. Scientific data included in published manuscripts will be available at the time of publication; all other generated scientific data will be shared no later than the end of the award. The study data will be stored in the repository for at least 5 years.
• Access Criteria: To request access of the data, researchers will use the standard processes at Dryad. Given that we seek the widest possible availability, in most cases all that is necessary is obtaining a Dryad account from the repository web site.

Locations

US (1)