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

NCT ID: NCT03414333

Last Updated: 2018-07-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-06-29
• Study Completion Date: 2018-06-30

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:

1. In obese subjects undergoing RYGB to test the effect of chronic elevation of GLP1 levels, and

2. 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.

Conditions

Glucose Metabolism Disorders; Obesity; Degenerative Brain Disorder

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

RYGB

Intervention Type: 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.

GLP-1

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

Group Type: ACTIVE_COMPARATOR

GLP-1

Intervention Type: DRUG

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

Interventions

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.

Intervention Type: PROCEDURE

GLP-1

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

Intervention Type: DRUG

Other Intervention Names

gut hormone

Eligibility Criteria

Inclusion Criteria

1. Males and females undergoing bariatric surgery as per clinical management

2. Age = 18-60 years

3. BMI>35 Kg/m 2 and stable weight (± 3 lbs) over the preceding three months

4. Normal Glucose Tolerance (HbA1c > 4.5 % and < 5.7%) or Type 2 diabetes (HbA1c >5.7 % and <10.0%)

5. Stable eGFR (>60 ml/min/1.73 m2 )

6. 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.

7. Subjects are capable of giving informed consent

1. Males and females

2. Age = 18-60 years

3. BMI 22-35 Kg/m 2 and stable weight (± 3 lbs) over the preceding three months

4. Stable eGFR (&gt;60 ml/min/1.73 m 2 )

5. Normal Glucose Tolerance (HbA1c>4.5 % and< 5.7%)

6. Subjects are capable of giving informed consent.

Exclusion Criteria

1. Steroids treatment

2. Psychiatric Disorders

3. Mental Retardation

4. Severe cognitive Impairment

5. Neurodegenerative diseases

6. Epilepsy

7. Depression Treatment

8. Traumatic Brain Injury over the preceding six months

9. Liver function enzymes higher more than two times the upper limit

10. Heart Failure (NYHA III-IV)

11. Type 1 Diabetes

12. Diabetic Ketoacidosis

13. GFR<60 ml/min/1.73 m 2

14. 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

15. Women who are pregnant or breastfeeding

16. 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Pisa

OTHER

Sponsor Role: lead

Responsible Party

Prof. Stefano Del Prato

Clinical Resercher

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Stefano Del Prato, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pisa

Locations

Dept.Clinical and Experimental Medicine.Section of Diabetes.

Pisa, , Italy

Countries

Italy

References

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.

Reference Type: DERIVED

PMID: 35729365 (View on PubMed)

Other Identifiers

PRA 2016

Identifier Type: -

Identifier Source: org_study_id