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

NCT03414333 | Completed

• 1 other identifier: PRA 2016
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

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.

Conditions

Glucose Metabolism Disorders; Obesity; Degenerative Brain Disorder

Keywords

obesity; cognitive dysfunction

Outcome Measures

Primary Outcomes (1)

• sustained Weight Loss

  normalizing obesity-related comorbidities.

  6 months

Secondary Outcomes (1)

• glycemic Control

  6 months

Other Outcomes (1)

• cognitive Function

  6 months

Study Arms (2)

Roux-en- Y gastric bypass (RYGB)

EXPERIMENTAL

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

GLP-1

ACTIVE COMPARATOR

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

Drug: GLP-1

Interventions

RYGB PROCEDURE

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.

Roux-en- Y gastric bypass (RYGB)

GLP-1 DRUG

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

Also known as: gut hormone

GLP-1

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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
• 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 (\&gt;60 ml/min/1.73 m 2 )
• Normal Glucose Tolerance (HbA1c\>4.5 % and\< 5.7%)
• Subjects are capable of giving informed consent.

You may not qualify if:

• 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 \&gt; 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

Sponsors & Collaborators

• University of Pisa: lead

Study Sites (1)

Dept.Clinical and Experimental Medicine.Section of Diabetes.

Pisa, Italy

Location

Related Publications (1)

• 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.

  PMID: 35729365 DERIVED

MeSH Terms

Conditions

Glucose Metabolism Disorders; Obesity; Cognitive Dysfunction

Interventions

Glucagon-Like Peptide 1

Condition Hierarchy (Ancestors)

Metabolic Diseases; Nutritional and Metabolic Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Stefano Del Prato, MD

  University of Pisa

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Resercher

Study Record Dates

• First Submitted: January 15, 2018
• First Posted: January 29, 2018
• Study Start: June 29, 2016
• Primary Completion: June 1, 2017
• Study Completion: June 1, 2018
• Last Updated: July 19, 2018

Record last verified: 2018-07

Locations

IT (1)