## Protocol Section
### Identification Module
**NCT ID:** NCT06424015

**Brief Title:** Insulin and Insulin Pulses During Fasting

**Official Title:** Effect of Insulin and Insulin Pulses on Fasting Glucagon Secretion and on Glucose Metabolism in Subjects Without Type 2 Diabetes

#### Organization Study ID Info
**ID:** 24-002631
#### Organization
**Class:** OTHER
**Full Name:** Mayo Clinic
### Status Module
#### Completion Date
**Date:** 2027-09-01

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-21

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-16

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2026-09-01

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-09-01

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-21
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-13
**Study First Submit QC Date:** 2024-05-16
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Mayo Clinic

#### Responsible Party

**Investigator Affiliation:** Mayo Clinic

**Investigator Full Name:** Adrian Vella

**Investigator Title:** Professor of Medicine

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** Fasting hyperglycemia contributes disproportionately to nonenzymatic glycosylation and the microvascular complications of type 2 diabetes. However, little is known about the regulation of glucose concentrations in the fasting state relative to what is known about the postprandial state. The proposed experiment is part of a series of experiments designed to establish how glucagon and insulin interact with their receptors to control fasting glucose in health and in prediabetes.

**Detailed Description:** Decreased insulin action increases glucagon concentrations. In rodents, insulin signaling restrains glucagon secretion. It is unclear if this is the case in all (subtypes of) prediabetes. Impaired hepatic insulin action exacerbates glucagon's effects on endogenous glucose production. Also, insulin resistance in the β-cell impairs negative feedback inhibition of insulin secretion. This leads to hyperinsulinemia in rodents and humans. How these variables interact is unknown. This experiment will determine how insulin variably regulates fasting glucagon (and insulin) secretion directly, or indirectly, in prediabetes.

The inability of the proinsulin to insulin ratio to reliably predict β-cell integrity, endoplasmic reticulum stress and β-cell function has led to the identification of novel markers of β-cell health. In addition, the relationship of glucagon and insulin pulses will be quantified. Preliminary data shows that there is heterogeneity in these relationships even in normal fasting glucose. Th experiment will also determine how islet hormone / glucose crosstalk and pulse characteristics contribute to prediabetes.

### Conditions Module

**Conditions:**

- PreDiabetes

**Keywords:**

- insulin secretion

- glucagon secretion

- endogenous glucose production

- glucose disappearance

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** CROSSOVER

##### Masking Info

**Masking:** NONE

**Primary Purpose:** BASIC_SCIENCE

#### Enrollment Info

**Count:** 60

**Type:** ESTIMATED

**Phases:**

- NA

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Between 0600 (-180 min) and 1300 (240 min) Intralipid (20%, 0.011ml/kg/min; Baxter, Healthcare, Deerfield, IL) and heparin (200 units prime, 0.2 unit/kg/min continuous) will be infused to induce acute insulin resistance.

**Intervention Names:**

- Other: Intralipid and heparin

**Label:** Intralipid and heparin

**Type:** ACTIVE_COMPARATOR

#### Arm Group 2

**Description:** Between 0600 (-180 min) and 1300 (240 min) saline will be infused

**Intervention Names:**

- Other: Saline

**Label:** Saline

**Type:** PLACEBO_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Intralipid and heparin

**Description:** Intralipid (20%, 0.011ml/kg/min; Baxter, Healthcare, Deerfield, IL) and heparin (200 units prime, 0.2 unit/kg/min continuous) will be infused to induce acute insulin resistance

**Name:** Intralipid and heparin

**Type:** OTHER

#### Intervention 2

**Arm Group Labels:**

- Saline

**Description:** Saline will be infused

**Name:** Saline

**Type:** OTHER

### Outcomes Module

#### Primary Outcomes

**Description:** comparison of EGP in people with IFG vs NFG in response to insulin infusion

**Measure:** Suppression of Endogenous glucose production (EGP) by insulin

**Time Frame:** The rate of EGP at 240 minutes (end of study) expressed as a percentage of fasting EGP (at the start of the study i.e.: 0 minutes.

**Description:** comparison of Insulin pulse orderliness measured by approximate entropy in people with IFG vs NFG

**Measure:** Insulin pulse orderliness

**Time Frame:** Approximate Entropy (ApEn) will be calculated from the insulin concentrations observed every 2 minutes between -45 and 0 minutes

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* people with normal or impaired fasting glucose and normal or impaired glucose tolerance

Exclusion Criteria:

1. HbA1c \> 6.5%
2. BMI ≥ 35 Kg/M2
3. Use of any glucose-lowering agents including metformin or sulfonylureas.
4. For female subjects: positive pregnancy test at the time of enrollment or study
5. History of prior upper abdominal surgery such as adjustable gastric banding, pyloroplasty and vagotomy.
6. Active systemic illness or malignancy.
7. Symptomatic macrovascular or microvascular disease.
8. Hematocrit \< 35%

**Healthy Volunteers:** True

**Maximum Age:** 65 Years

**Minimum Age:** 25 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** Osmundson.Kimberly@mayo.edu

**Name:** Kim Osmundson, CCRP

**Phone:** 507-255-0907

**Role:** CONTACT

**Contact 2:**

**Email:** Laugen.Jeanette@mayo.edu

**Name:** Jeanette Laugen

**Phone:** 507-255-8110

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Rochester

**Country:** United States

**Facility:** Mayo Clinic in Rochester

**State:** Minnesota

**Zip:** 55905

#### Overall Officials

**Official 1:**

**Affiliation:** Mayo Clinic

**Name:** Adrian Vella, MD

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**Access Criteria:** The data being shared is human data from clinical trials and therefore a higher level of protection is required. Access to this data will be controlled by a managed access process whereby access is provided only after approval. Data will be controlled access with the General Research Use Data Use Limitation, as allowed by the informed consent and the institutional certification.

**Description:** Data that will be preserved and shared include results of screening labs, immunoassay data and glucose turnover data. In addition, we will share the study protocol, statistical analysis plan, a data dictionary and anonymization guidance (methodology to anonymize data).In addition to the patient-level data, the metadata, data dictionary, statistical analysis plan, and final protocol will be shared. The sharing of the data dictionary, statistical analysis plan and final protocol with amendments will enable researchers to understand how the data was collected and to correctly interpret the data for future secondary analysis. The final patient level dataset will include demographics as well as screening data and primary and secondary outcomes.We plan to share datasets resulting from the proposed studies in Vivli, a non-profit institution that supports the Vivli repository.

**Info Types:**

- STUDY_PROTOCOL

- SAP

- ICF

- CSR

- ANALYTIC_CODE

**IPD Sharing:** YES

**Time Frame:** The data shared will be archived and available on the platform for request by researchers for a minimum of 10 years after contribution. Data will be made accessible no later than the time of our associated publication or the end of the grant period (whichever comes first). On an ongoing basis, Vivli evaluates its data holdings regarding maintaining access and reserves the right to discontinue the distribution of a data collections when deemed appropriate. When materials are deaccessioned, the data are no longer publicly accessible at Vivli, they may still be preserved in Vivli's storage vault. Because digital files are assigned a persistent digital object identifier (DOI), the study description is still available to view, but is not searchable through Vivli.

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000003920

- Term: Diabetes Mellitus

- ID: D000044882

- Term: Glucose Metabolism Disorders

- ID: D000008659

- Term: Metabolic Diseases

- ID: D000004700

- Term: Endocrine System Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC18

- Name: Nutritional and Metabolic Diseases

- Abbrev: BC19

- Name: Gland and Hormone Related Diseases

- Abbrev: All

- Name: All Conditions

### Condition Browse Module - Browse Leaves

- ID: M14117

- Name: Prediabetic State

- Relevance: HIGH

- As Found: Prediabetes

- ID: M20295

- Name: Glucose Intolerance

- Relevance: LOW

- As Found: Unknown

- ID: M7115

- Name: Diabetes Mellitus

- Relevance: LOW

- As Found: Unknown

- ID: M7119

- Name: Diabetes Mellitus, Type 2

- Relevance: LOW

- As Found: Unknown

- ID: M11639

- Name: Metabolic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M25403

- Name: Glucose Metabolism Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M7862

- Name: Endocrine System Diseases

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000011236

- Term: Prediabetic State

### Intervention Browse Module - Ancestors

- ID: D000000925

- Term: Anticoagulants

- ID: D000005343

- Term: Fibrinolytic Agents

- ID: D000050299

- Term: Fibrin Modulating Agents

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

- ID: D000005217

- Term: Fat Emulsions, Intravenous

- ID: D000057947

- Term: Parenteral Nutrition Solutions

- ID: D000019999

- Term: Pharmaceutical Solutions

### Intervention Browse Module - Browse Branches

- Abbrev: Hypo

- Name: Hypoglycemic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: Gast

- Name: Gastrointestinal Agents

- Abbrev: FiAg

- Name: Fibrinolytic Agents

- Abbrev: AnCoag

- Name: Anticoagulants

- Abbrev: PhSol

- Name: Pharmaceutical Solutions

- Abbrev: HB

- Name: Herbal and Botanical

### Intervention Browse Module - Browse Leaves

- ID: M10365

- Name: Insulin

- Relevance: LOW

- As Found: Unknown

- ID: M173166

- Name: Insulin, Globin Zinc

- Relevance: LOW

- As Found: Unknown

- ID: M9043

- Name: Glucagon

- Relevance: LOW

- As Found: Unknown

- ID: M9579

- Name: Heparin

- Relevance: HIGH

- As Found: Obesity

- ID: M46053

- Name: Calcium heparin

- Relevance: LOW

- As Found: Unknown

- ID: M26997

- Name: Glucagon-Like Peptide 1

- Relevance: LOW

- As Found: Unknown

- ID: M223889

- Name: Soybean oil, phospholipid emulsion

- Relevance: HIGH

- As Found: 5000

- ID: M4244

- Name: Anticoagulants

- Relevance: LOW

- As Found: Unknown

- ID: M8473

- Name: Fibrinolytic Agents

- Relevance: LOW

- As Found: Unknown

- ID: M8360

- Name: Fat Emulsions, Intravenous

- Relevance: LOW

- As Found: Unknown

- ID: M21860

- Name: Pharmaceutical Solutions

- Relevance: LOW

- As Found: Unknown

- ID: M28934

- Name: Parenteral Nutrition Solutions

- Relevance: LOW

- As Found: Unknown

- ID: T294

- Name: Soy Bean

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000006493

- Term: Heparin

- ID: C000545823

- Term: Soybean oil, phospholipid emulsion

### Misc Info Module

- Version Holder: 2024-05-31
