Long-acting Exenatide and Cognitive Decline in Dysglycemic Patients (DRINN)

August 10, 2021 updated by: Alessandra Dei Cas, Azienda Ospedaliero-Universitaria di Parma

Long-acting Exenatide: a Tool to Stop Cognitive Decline in Dysglycemic Patients With Mild Cognitive Impairment?

The overall objective of the study is to assess the potential effects of the long-acting GLP-1 analogue exenatide in preventing/slowing the progression of cognitive dysfunction and related biomarkers in dysglycemic/prediabetic patients with mild cognitive impairment (MCI).

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

Type 2 Diabetes Mellitus (T2DM) and Alzheimer's Disease (AD) are two of the most common diseases of aging.The presence of T2DM almost doubles the risk of developing AD and is associated with a faster rate of cognitive decline in those with mild cognitive impairment (MCI). Blood glucose levels are directly associated with accelerated cognitive decline also in subjects with impaired fasting glucose and in individuals without clinical DM. Impaired insulin signaling is critically involved in the natural history of both T2DM and AD and it may represent a common mechanistic link ("common soil") between dysglycemic/prediabetic states and AD development and progression.

The overall objective of the study is to assess the potential effects of the long-acting GLP-1 analogue exenatide in preventing/slowing the progression of cognitive dysfunction and related biomarkers in dysglycemic/prediabetic patients with mild cognitive impairment (MCI).

All eligible patients at V0 will undergo baseline assessments (V1) and will be allocated according to the procedure of randomization to one of the study arms. Follow-up (FU) visits for all subjects will be at 16 (V2) and at 32 weeks (V3) after randomization. Additionally, subjects on active treatment will be admitted weekly to the Outpatient Diabetes Unit of the AOUPR for GLP-1 subcutaneous injections and to check for possible side effects. Subjects in the control arm will be seen at the Center for Dementia (AOUPR) according to their usual schedule.

Laboratory and diagnostic:

At each study visits patients will undergo:

  • anthropometric and hemodynamic assessment: weight and height for Body Mass Index (BMI) calculation, waist circumference, ambulatory blood pressure, heart rate;
  • blood test collection of metabolic profile: blood collection for metabolic/hormonal profile: fasting plasma glucose, HbA1c, insulin, C-peptide, glucagon, active GLP-1, total gastric inhibitory polypeptide (GIP), total cholesterol, HDL-cholesterol, triglycerides, AST, ALT, pancreatic amylase, lipase, creatinine, eGFR.
  • cognitive function tests: ADAS-cog and the quality score of MMSE, Phonemic verbal fluency test; Semantic verbal fluency test; Geriatric Depression Scale (GDS) ; Clinical Dementia Rating Scale (CDR); Neuropsychiatric Inventory (NPI); Activities of Daily Living (ADL); Instrumental Activities of Daily Living (IADL).

ADAS-cog was designed to measure the severity of the most important symptoms of Alzheimer's disease. It consists of 11 7 tasks measuring the disturbances of memory, language, praxis, attention and other cognitive abilities which are often referred to as the core symptoms of AD.

- Functional Magnetic Resonance Imaging (MRI)(only at V1 and V3).

Study Type

Interventional

Enrollment (Anticipated)

40

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Parma, Italy, 43126
        • Endocrinology Unit
      • Parma, Italy
        • Center for Cognitive Disorders and Dementia AUSL of Parma and University of Parma

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

51 years to 79 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • patients capable of giving informed consent
  • dysglycemia/prediabetes defined as fasting plasma glucose between 100 and 125 mg/dl and/or 2-hour plasma glucose between 140 and 199 mg/dl after a 75 g OGTT and/or a HbA1c value between 5.7 and 6.4%
  • diagnosis of MCI according to the Petersen clinical criteria (the expected corrected scores at the MMSE are from 24 to 27)
  • age >50<80 yrs
  • stable medication for the past 3 months
  • Caucasian ethnicity

Exclusion Criteria:

  • age <50>80 yrs
  • incapability to give informed consent
  • diabetes defined according to American Diabetes Association (ADA) criteria
  • clinically significant liver or kidney dysfunction defined as s-ALT > 2 times upper reference or estimated creatinine-clearance (eGFR) < 60 mL / min/1.73m2, assessed by with CKD-EPI formula
  • endocrinological diseases other than well controlled hypothyroidism, personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia (MEN) syndrome, severe gastro-intestinal diseases (i.e gastroparesis, dumping syndromes), current or history of chronic or acute pancreatitis
  • any contraindication to the use of exenatide as per the Summary of Product Characteristics
  • known abuse of alcohol or drugs
  • ferro-magnetic prosthesis, pacemaker or other metals incorporated in the body
  • significant neurologic disease other than MCI (i.e. Parkinson's disease, multiple system atrophy, normal pressure hydrocephalus, progressive supranuclear palsy, subarachnoid hemorrhage, brain neoplasms, Huntington disease, epilepsy or head trauma)
  • BMI ≤22 Kg/m2 in subject ≥ 70 yrs
  • MRI/CT showing unambiguous etiological evidence of cerebrovascular disease with regard to MCI
  • severe sensory defects; current presence of clinically significant psychiatric disorder
  • warfarin treatment, clinically significant systemic condition
  • history of cancer within the last 5 yrs
  • known allergy to exenatide or any of the other components.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: exenatide
long-acting exenatide 2 mg subcutaneously once-weekly
Drug: Exenatide
Patients will be injected subcutaneously 2 mg long-acting exenatide once-weekly. No dose titration is foreseen.
Other Names:
  • bydureon
Placebo Comparator: placebo
no drug assigned
Other: placebo
patients will be seen at the Center for Cognitive Disorders and Dementia according to their usual schedule.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Improvement of ADAS-cog Alzheimer's Disease Assessment Scale defined by ADAS-cog score at 16 (V2) and at 32 weeks (V3) compared to baseline
Time Frame: 16 and 32 weeks
Absolute difference in the ADAS-Cog score compared to baseline in the 2 arms.
16 and 32 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Improvement of Mini Mental State Evaluation test at 16 (V2) and at 32 weeks (V3) compared to baseline
Time Frame: 16 and 32 weeks
Absolute difference in the Mini Mental State Evaluation (MMSE) score compared to baseline in the 2 arms.
16 and 32 weeks
Improvement of Mini Mental State Evaluation quality test at 16 (V2) and at 32 weeks (V3) compared to baseline
Time Frame: 16 and 32 weeks
Absolute difference in the MMSE quality test score compared to baseline in the 2 arms.
16 and 32 weeks
Improvement of Phonemic verbal fluency test at 16 (V2) and at 32 weeks (V3) compared to baseline
Time Frame: 16 and 32 weeks
Absolute difference in the Phonemic verbal fluency test score compared to baseline in the 2 arms.
16 and 32 weeks
Improvement of Semantic verbal fluency test at 16 (V2) and at 32 weeks (V3) compared to baseline
Time Frame: 16 and 32 weeks
Absolute difference in the Semantic verbal fluency test score compared to baseline in the 2 arms.
16 and 32 weeks
Improvement of Geriatric Depression Scale (GDS) test at 16 (V2) and at 32 weeks (V3) compared to baseline
Time Frame: 16 and 32 weeks
Absolute difference in the GDS test score compared to baseline in the 2 arms.
16 and 32 weeks
Improvement of Clinical Dementia Rating Scale (CDR) test at 16 (V2) and at 32 weeks (V3) compared to baseline
Time Frame: 16 and 32 weeks
Absolute difference in the CDR test score compared to baseline in the 2 arms.
16 and 32 weeks
Improvement of Neuropsychiatric Inventory (NPI) test at 16 (V2) and at 32 weeks (V3) compared to baseline
Time Frame: 16 and 32 weeks
Absolute difference in the NPI test score compared to baseline in the 2 arms.
16 and 32 weeks
Improvement of Activities of Daily Living (ADL) test at 16 (V2) and at 32 weeks (V3) compared to baseline
Time Frame: 16 and 32 weeks
Absolute difference in the ADL test score compared to baseline in the 2 arms.
16 and 32 weeks
Improvement of Instrumental Activities of Daily Living (IADL) test at 16 (V2) and at 32 weeks (V3) compared to baseline
Time Frame: 16 and 32 weeks
Absolute difference in the IADL test score compared to baseline in the 2 arms.
16 and 32 weeks
changes in structural and functional connectivity of neural networks as assessed by functional MRI (fMRI) at 16 (V2) and at 32 weeks (V3)
Time Frame: 16 and 32 weeks
Before and after treatment voxel-wise brain maps will be statistically compared using Statistical Parametric Mapping, by a multivariate 2 x 2 ANOVA (experimental treatment /placebo x time pre/post) in order to observe changes in structural and functional connectivity of neural networks in relation to treatment
16 and 32 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Azienda Ospedaliero-Universitaria di Parma

Investigators

  • Principal Investigator: Alessandra Dei Cas, MD, Azienda Ospedaliero-Universitaria di Parma

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2016

Primary Completion (Actual)

July 1, 2019

Study Completion (Anticipated)

October 31, 2021

Study Registration Dates

First Submitted

July 21, 2016

First Submitted That Met QC Criteria

July 27, 2016

First Posted (Estimate)

July 28, 2016

Study Record Updates

Last Update Posted (Actual)

August 17, 2021

Last Update Submitted That Met QC Criteria

August 10, 2021

Last Verified

August 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2015-001850-13

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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