Investigating Whether Acute Elevation of Fatty Acid Levels Alters Cerebral Glucose Transport and Metabolism

Sponsor

Yale University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04328337

Collaborator

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)

Enrollment

Location

Arms

45.7

Anticipated Duration (Months)

0.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The goal of this study is to understand the role of brain glucose transport in individuals with obesity and the association with cerebral hypometabolism and these individuals' response to plasma glucose elevations. The main premise is that obesity leads to reduced brain glucose transport and that we can measure this reduction with magnetic resonance spectroscopy (MRS). The secondary premises are that this reduction is driven by elevated non esterified fatty acids which act to turn on specific signaling pathways that regulate brain GLUT1 levels.

Condition or Disease	Intervention/Treatment	Phase
Obesity	Drug: Intralipid, 20% Intravenous Emulsion Drug: Placebos	Phase 1/Phase 2

Detailed Description

There are 2 aims of this study. The intent of aim 1 is to measure the effect of obesity on glucose transport and metabolism in the human brain. This study aim will be conducted in non-diabetic, obese individuals and age- and HbA1c-matched normal weight individuals. A total of 15 non-diabetic - normal weight individuals and 15 obese individuals will be enrolled.

The second aim randomizes 40 non-diabetic, normal weight individuals. The intent of aim 2 is to determine whether acute elevation of NEFA levels in lean, healthy individuals will alter cerebral glucose transport. Eligible participants will be randomized (1:1) to receive either intralipid or normal saline.

The focus of this protocol registration is the randomized portion of the study (aim 2).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Participant)

Primary Purpose:

Diagnostic

Official Title:

Investigating Whether Acute Elevation of Fatty Acid Levels Alters Cerebral Glucose Transport and Metabolism

Actual Study Start Date :

Dec 8, 2020

Anticipated Primary Completion Date :

Sep 30, 2024

Anticipated Study Completion Date :

Sep 30, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Non-diabetic, normal weight individuals receiving Intralipid Non-diabetic, normal weight individuals receiving Intralipid. Participants will receive an infusion of Intralipid 20% for 12 hours through an IV (prior to and during scan #2)	Drug: Intralipid, 20% Intravenous Emulsion Infusion of Intralipid 20%
Placebo Comparator: Non-diabetic, normal weight individuals receiving saline Non-diabetic, normal weight individuals receiving saline. Participants will receive an infusion of normal saline (1:1 randomization) at 30 ml/hr for 12 hours through an IV (prior to and during scan #2	Drug: Placebos saline 30 ml/hr for 12 hours through an IV

Arm

Intervention/Treatment

Experimental: Non-diabetic, normal weight individuals receiving Intralipid

Non-diabetic, normal weight individuals receiving Intralipid. Participants will receive an infusion of Intralipid 20% for 12 hours through an IV (prior to and during scan #2)

Drug: Intralipid, 20% Intravenous Emulsion

Infusion of Intralipid 20%

Placebo Comparator: Non-diabetic, normal weight individuals receiving saline

Non-diabetic, normal weight individuals receiving saline. Participants will receive an infusion of normal saline (1:1 randomization) at 30 ml/hr for 12 hours through an IV (prior to and during scan #2

Drug: Placebos

saline 30 ml/hr for 12 hours through an IV

Outcome Measures

Primary Outcome Measures

Change in brain glucose transport capacity [Through End of Study (Up to 12 hours)]
Measurement of brain glucose transport rates using magnetic resonance spectroscopy (MRS).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 45 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Age 18-45 years
HbA1C <6.5%
Normal weight individuals: BMI 17-25 kg/m2
Obese individuals: BMI >30 kg/m2

Exclusion Criteria:

Creatinine >1.5mg/dL
Hematocrit <35% for females and <39% for males
ALT and AST >2.5X upper limit of normal
Abnormal TSH
Abnormal PT/PTT/INR
Triglycerides >200 mg/dL
Known hepatic, gastrointestinal, renal, neurologic, psychiatric, cerebrovascular disease
Uncontrolled hypertension
Current or past 3 months use of ketogenic diet
Use of any medications, vitamins, or supplements that can alter cerebral metabolism or lipids
Smoking
Current or recent steroid use in last 6 months
5% body weight change in last 6 months
Illicit drug use/alcoholism
Inability to enter MRI/MRS
For women: pregnancy, seeking pregnancy, or breastfeeding

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Yale School of Medicine	New Haven	Connecticut	United States	06519

Sponsors and Collaborators

Yale University
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

Principal Investigator: Janice Hwang, MD, Yale University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Yale University

ClinicalTrials.gov Identifier:

NCT04328337

Other Study ID Numbers:

2000026149
1R01DK123227-01

First Posted:

Mar 31, 2020

Last Update Posted:

May 19, 2022

Last Verified:

May 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Soybean oil, phospholipid emulsion

Study Results

No Results Posted as of May 19, 2022