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To Determine the Effect of GLP1 on Cognitive Function, Brain Glucose Metabolism and Neuroplasticity.

Primary Purpose

Glucose Metabolism Disorders, Obesity, Degenerative Brain Disorder

Status

Completed

Phase

Not Applicable

Locations

Italy

Study Type

Interventional

Intervention

RYGB

GLP-1

About this trial

This is an interventional treatment trial for Glucose Metabolism Disorders focused on measuring obesity, cognitive dysfunction

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:(Morbid Obese Subjects Group)

Males and females undergoing bariatric surgery as per clinical management
Age = 18-60 years
BMI>35 Kg/m 2 and stable weight (± 3 lbs) over the preceding three months
Normal Glucose Tolerance (HbA1c > 4.5 % and < 5.7%) or Type 2 diabetes (HbA1c >5.7 % and <10.0%)
Stable eGFR (>60 ml/min/1.73 m2 )
Drug naive for type 2 diabetes treatment or on stable dose more than 3 months with anti-diabetic agents other than DPP4-inhibitors, GLP1 receptor agonists, and insulin.
Subjects are capable of giving informed consent

Inclusion Criteria (Healthy Subjects Group)

Males and females
Age = 18-60 years
BMI 22-35 Kg/m 2 and stable weight (± 3 lbs) over the preceding three months
Stable eGFR (>60 ml/min/1.73 m 2 )
Normal Glucose Tolerance (HbA1c>4.5 % and< 5.7%)
Subjects are capable of giving informed consent.

Exclusion Criteria:(both groups)

Steroids treatment
Psychiatric Disorders
Mental Retardation
Severe cognitive Impairment
Neurodegenerative diseases
Epilepsy
Depression Treatment
Traumatic Brain Injury over the preceding six months
Liver function enzymes higher more than two times the upper limit
Heart Failure (NYHA III-IV)
Type 1 Diabetes
Diabetic Ketoacidosis
GFR<60 ml/min/1.73 m 2
Donation of blood to a blood bank, blood transfusion, or participation in a clinical study requiring withdrawal of > 400 mL of blood during the 8 weeks prior to the enrollment visit and at least 8 weeks thereafter
Women who are pregnant or breastfeeding
Patient with a history or current evidence of any condition, therapy, laboratory abnormality, or other circumstance which, in the opinion of the investigator or coordinator, might pose an unacceptable risk to the patient or interfere with trial procedures.

Sites / Locations

Dept.Clinical and Experimental Medicine.Section of Diabetes.

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Roux-en- Y gastric bypass (RYGB)

GLP-1

Arm Description

Roux-en- Y gastric bypass (RYGB) is the most popular bariatric procedure and it has been associated with improvements in glycemic control and cognitive function. It works by decreasing the amount of food you can eat at one sitting and by changing the hormones released at the bottom of the stomach and duodenum.we propose that RYGB is a model of chronic elevation of GLP-1 providing an opportunity to explore relationship between changes in the circulating hormone and brain glucose metabolism, cognitive function and neuroplasticity.

GLP-1 is an intestinal hormone secreted in response to nutrients.

Outcomes

Primary Outcome Measures

sustained Weight Loss

normalizing obesity-related comorbidities.

Secondary Outcome Measures

glycemic Control

GLP-1 level controled

Full Information

NCT ID

NCT03414333

First Posted

January 15, 2018

Last Updated

July 18, 2018

Sponsor

University of Pisa

1. Study Identification

Unique Protocol Identification Number

NCT03414333

Brief Title

To Determine the Effect of GLP1 on Cognitive Function, Brain Glucose Metabolism and Neuroplasticity.

Official Title

The Effect of Glucagon-like Peptide-1 (GLP-1) on Cognitive and Non-cognitive Function in Human

Study Type

Interventional

2. Study Status

Record Verification Date

July 2018

Overall Recruitment Status

Completed

Study Start Date

June 29, 2016 (Actual)

Primary Completion Date

June 2017 (Actual)

Study Completion Date

June 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Pisa

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief Summary

To test the hypothesis that GLP1 can exert favourable effects on multiple aspects of brain function. To this purpose, the investigator determine whether chronic increase in GLP1 concentration as it occurs after bariatric surgery (Roux-en- Y Gastric Bypass) is associated with improvement in: cognitive function measured by Mini Mental State Examination (MMSE) and Mental Deterioration Battery(MDB). brain glucose metabolism measured by FDG-CT/PET neuroplasticity measure by binocular rivalry and saccadic adaptation tests in morbid obese subjects. In order to discern the effect of GLP1 irrespective of changes in the metabolic milieu the investigator will test whether short-term GLP-1 infusion can modulate the same parameters in healthy subjects.

Detailed Description

The research project will include two separate studies: In obese subjects undergoing RYGB to test the effect of chronic elevation of GLP1 levels, and In normal volunteers to test the acute effect of GLP1, irrespective of changes in the metabolic milieu In several aspects of brain function as detailed below:. Morbid Obese Subjects Group: This study will consist in a single arm, non randomized, uncontrolled, single center before-and after RYGB in 15 morbid obese subjects. Healthy Subjects Group: This study will consist in a single arm, non randomized, uncontrolled, single center study in 8 healthy subjects. The primary endpoint are the changes in: cognitive function measured by Mini Mental State Examination (MMSE) and Mental Deterioration Battery (MDB) brain glucose metabolism measured by FDG-CT/PET neuroplasticity measure by binocular rivalry and saccadic adaptation tests six months after RYGB in morbid obese subjects and with elevation of circulating GLP1 levels in healthy subjects. Morbid obese subjects participating in this study will be evaluated before and 6 months after bariatric surgery which is routinely performed to treat morbid obesity. For the purpose of baseline assessment subjects will undergo 3 visits at 1 week interval. All test procedures will be repeated in two subsequent visits 6 months after surgery with body weight being stable. Therefore, participation in the study will require a total of 5 visit with a post-trial phone contact 2 weeks after completion for safety assessment. Healthy subjects will be recruited for determining the acute effect of GLP1 on brain function irrespective of changes in the metabolic milieu. The study will require participation in a total of 3 visits.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Glucose Metabolism Disorders, Obesity, Degenerative Brain Disorder

Keywords

obesity, cognitive dysfunction

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

14 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Roux-en- Y gastric bypass (RYGB)

Arm Type

Experimental

Arm Description

Arm Title

GLP-1

Arm Type

Active Comparator

Arm Description

GLP-1 is an intestinal hormone secreted in response to nutrients.

Intervention Type

Procedure

Intervention Name(s)

RYGB

Intervention Description

RYGB is associated with a increase of circulating GLP-1 (up to ten-fold) especially in response to meal ingestion. This increased availability of GLP1 has been claimed to contribute to restoration of some of the beta-cell function.

Intervention Type

Drug

Intervention Name(s)

GLP-1

Other Intervention Name(s)

gut hormone

Intervention Description

GLP-1 is an hormone secreted by gut in response to nutrients ingestion.

Primary Outcome Measure Information:

Title

sustained Weight Loss

Description

normalizing obesity-related comorbidities.

Time Frame

6 months

Secondary Outcome Measure Information:

Title

glycemic Control

Description

GLP-1 level controled

Time Frame

6 months

Other Pre-specified Outcome Measures:

Title

cognitive Function

Description

cognitive function measured by Mini Mental State Examination (MMSE).

Time Frame

6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria:(Morbid Obese Subjects Group) Males and females undergoing bariatric surgery as per clinical management Age = 18-60 years BMI>35 Kg/m 2 and stable weight (± 3 lbs) over the preceding three months Normal Glucose Tolerance (HbA1c > 4.5 % and < 5.7%) or Type 2 diabetes (HbA1c >5.7 % and <10.0%) Stable eGFR (>60 ml/min/1.73 m2 ) Drug naive for type 2 diabetes treatment or on stable dose more than 3 months with anti-diabetic agents other than DPP4-inhibitors, GLP1 receptor agonists, and insulin. Subjects are capable of giving informed consent Inclusion Criteria (Healthy Subjects Group) Males and females Age = 18-60 years BMI 22-35 Kg/m 2 and stable weight (± 3 lbs) over the preceding three months Stable eGFR (>60 ml/min/1.73 m 2 ) Normal Glucose Tolerance (HbA1c>4.5 % and< 5.7%) Subjects are capable of giving informed consent. Exclusion Criteria:(both groups) Steroids treatment Psychiatric Disorders Mental Retardation Severe cognitive Impairment Neurodegenerative diseases Epilepsy Depression Treatment Traumatic Brain Injury over the preceding six months Liver function enzymes higher more than two times the upper limit Heart Failure (NYHA III-IV) Type 1 Diabetes Diabetic Ketoacidosis GFR<60 ml/min/1.73 m 2 Donation of blood to a blood bank, blood transfusion, or participation in a clinical study requiring withdrawal of > 400 mL of blood during the 8 weeks prior to the enrollment visit and at least 8 weeks thereafter Women who are pregnant or breastfeeding Patient with a history or current evidence of any condition, therapy, laboratory abnormality, or other circumstance which, in the opinion of the investigator or coordinator, might pose an unacceptable risk to the patient or interfere with trial procedures.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Stefano Del Prato, MD

Organizational Affiliation

University of Pisa

Official's Role

Principal Investigator

Facility Information:

Facility Name

Dept.Clinical and Experimental Medicine.Section of Diabetes.

City

Pisa

Country

Italy

12. IPD Sharing Statement

Citations:

PubMed Identifier

35729365

Citation

Dardano A, Aghakhanyan G, Moretto C, Ciccarone A, Bellini R, Sancho Bornez V, Ceccarini G, Santini F, Volterrani D, Del Prato S, Daniele G. Brain effect of bariatric surgery in people with obesity. Int J Obes (Lond). 2022 Sep;46(9):1671-1677. doi: 10.1038/s41366-022-01162-8. Epub 2022 Jun 21.

Results Reference

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To Determine the Effect of GLP1 on Cognitive Function, Brain Glucose Metabolism and Neuroplasticity.

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