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

Sponsor

University of Pisa (Other)

Overall Status

Completed

CT.gov ID

NCT03414333

Collaborator

(none)

Enrollment

Location

Arms

23.1

Actual Duration (Months)

0.6

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Glucose Metabolism Disorders Obesity Degenerative Brain Disorder	Procedure: RYGB Drug: GLP-1	N/A

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

14 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jun 29, 2016

Actual Primary Completion Date :

Jun 1, 2017

Actual Study Completion Date :

Jun 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Roux-en- Y gastric bypass (RYGB) 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.	Procedure: RYGB 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.
Active Comparator: GLP-1 GLP-1 is an intestinal hormone secreted in response to nutrients.	Drug: GLP-1 GLP-1 is an hormone secreted by gut in response to nutrients ingestion. Other Names: gut hormone

Arm

Intervention/Treatment

Experimental: Roux-en- Y gastric bypass (RYGB)

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.

Procedure: RYGB

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.

Active Comparator: GLP-1

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

Drug: GLP-1

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

Other Names:

gut hormone

Outcome Measures

Primary Outcome Measures

sustained Weight Loss [6 months]
normalizing obesity-related comorbidities.

Secondary Outcome Measures

glycemic Control [6 months]
GLP-1 level controled

Other Outcome Measures

cognitive Function [6 months]
cognitive function measured by Mini Mental State Examination (MMSE).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts 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.