Status unknownNCT02847403DRINNUpdated Aug 17, 2021

Long-acting Exenatide and Cognitive Decline in Dysglycemic Patients

A Phase 3 interventional study of Exenatide and placebo in Dysglycemia and Cognitive Deficit, sponsored by Azienda Ospedaliero-Universitaria di Parma. Status unknown at 2 sites in Italy. Open to participants aged 51 Years to 79 Years. Per ClinicalTrials.gov, last updated 2021-08-17.

Sponsored by Azienda Ospedaliero-Universitaria di Parma · Phase 3, Interventional, and Treatment

The sponsor has not verified this record recently (last verified Aug 2021), so the status shown — last known as Active, not recruiting — may be out of date.

Phase: Phase 3
Study type: Interventional
Enrollment: 40
Allocation: Randomized
Ages: 51 Years to 79 Years
Sex: All

Study summary

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).

Read the 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.

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).

Conditions studied

Dysglycemia
Cognitive Deficit

Browse trials for

Cognition Disorders 419

Keywords

dysglycemia
MCI
exenatide LAR
GLP-1

In context

Cognition Disorders

419 studies on the registry are indexed under Cognition Disorders; 89 are open to participants now.

This study's planned enrollment of 40 is below the median of 60 across 294 interventional studies indexed under Cognition Disorders.

Browse Cognition Disorders studies →

Lead sponsor

Azienda Ospedaliero-Universitaria di Parma is the lead sponsor of 44 studies on the registry; 13 are open to participants now.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 51 Years to 79 Years
Sexes eligible: All
Accepts healthy volunteers: No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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

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 design

Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 40 participants (estimated)

Study arms

Experimental
exenatide
long-acting exenatide 2 mg subcutaneously once-weekly
Drug: Exenatide
Placebo comparator
placebo
no drug assigned
Other: placebo

Interventions

DrugExenatide
Patients will be injected subcutaneously 2 mg long-acting exenatide once-weekly. No dose titration is foreseen.
Also known as: bydureon
Otherplacebo
patients will be seen at the Center for Cognitive Disorders and Dementia according to their usual schedule.

What researchers measure

Primary outcomes

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
Absolute difference in the ADAS-Cog score compared to baseline in the 2 arms.
Time frame: 16 and 32 weeks

Secondary outcomes

Improvement of Mini Mental State Evaluation test at 16 (V2) and at 32 weeks (V3) compared to baseline
Absolute difference in the Mini Mental State Evaluation (MMSE) score compared to baseline in the 2 arms.
Time frame: 16 and 32 weeks
Improvement of Mini Mental State Evaluation quality test at 16 (V2) and at 32 weeks (V3) compared to baseline
Absolute difference in the MMSE quality test score compared to baseline in the 2 arms.
Time frame: 16 and 32 weeks
Improvement of Phonemic verbal fluency test at 16 (V2) and at 32 weeks (V3) compared to baseline
Absolute difference in the Phonemic verbal fluency test score compared to baseline in the 2 arms.
Time frame: 16 and 32 weeks
Improvement of Semantic verbal fluency test at 16 (V2) and at 32 weeks (V3) compared to baseline
Absolute difference in the Semantic verbal fluency test score compared to baseline in the 2 arms.
Time frame: 16 and 32 weeks
Improvement of Geriatric Depression Scale (GDS) test at 16 (V2) and at 32 weeks (V3) compared to baseline
Absolute difference in the GDS test score compared to baseline in the 2 arms.
Time frame: 16 and 32 weeks
Improvement of Clinical Dementia Rating Scale (CDR) test at 16 (V2) and at 32 weeks (V3) compared to baseline
Absolute difference in the CDR test score compared to baseline in the 2 arms.
Time frame: 16 and 32 weeks
Improvement of Neuropsychiatric Inventory (NPI) test at 16 (V2) and at 32 weeks (V3) compared to baseline
Absolute difference in the NPI test score compared to baseline in the 2 arms.
Time frame: 16 and 32 weeks
Improvement of Activities of Daily Living (ADL) test at 16 (V2) and at 32 weeks (V3) compared to baseline
Absolute difference in the ADL test score compared to baseline in the 2 arms.
Time frame: 16 and 32 weeks
Improvement of Instrumental Activities of Daily Living (IADL) test at 16 (V2) and at 32 weeks (V3) compared to baseline
Absolute difference in the IADL test score compared to baseline in the 2 arms.
Time frame: 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)
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
Time frame: 16 and 32 weeks

Study locations

2 sites

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

References and documents

Publications

Perry T, Holloway HW, Weerasuriya A, Mouton PR, Duffy K, Mattison JA, Greig NH. Evidence of GLP-1-mediated neuroprotection in an animal model of pyridoxine-induced peripheral sensory neuropathy. Exp Neurol. 2007 Feb;203(2):293-301. doi: 10.1016/j.expneurol.2006.09.028. Epub 2006 Nov 22. PubMed 17125767 ↗
During MJ, Cao L, Zuzga DS, Francis JS, Fitzsimons HL, Jiao X, Bland RJ, Klugmann M, Banks WA, Drucker DJ, Haile CN. Glucagon-like peptide-1 receptor is involved in learning and neuroprotection. Nat Med. 2003 Sep;9(9):1173-9. doi: 10.1038/nm919. Epub 2003 Aug 17. PubMed 12925848 ↗
McClean PL, Holscher C. Liraglutide can reverse memory impairment, synaptic loss and reduce plaque load in aged APP/PS1 mice, a model of Alzheimer's disease. Neuropharmacology. 2014 Jan;76 Pt A:57-67. doi: 10.1016/j.neuropharm.2013.08.005. Epub 2013 Aug 21. PubMed 23973293 ↗
Aviles-Olmos I, Dickson J, Kefalopoulou Z, Djamshidian A, Ell P, Soderlund T, Whitton P, Wyse R, Isaacs T, Lees A, Limousin P, Foltynie T. Exenatide and the treatment of patients with Parkinson's disease. J Clin Invest. 2013 Jun;123(6):2730-6. doi: 10.1172/JCI68295. PubMed 23728174 ↗

Individual participant data

Plan to share: Yes

Timeline

Tracking since Sep 25, 2026

Not marked actual or estimatedDates not marked actual or estimated

The record gives a start of Feb 2016, a primary completion of Jul 2019 and a completion of Oct 2021. It does not say whether these dates are actual or estimated.

How these figures are worked out, and which studies are left out of them.

Registered: Jul 21, 2016
First posted: Jul 28, 2016
Start: Feb 2016
Primary completionActual: Jul 2019
CompletionEst.: Oct 31, 2021
Last update: Aug 17, 2021

What these dates mean

Start.: When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.: When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.: When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.: Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.

No changes since tracking began. The registry record was last updated on Aug 17, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT02847403
Lead sponsor: Azienda Ospedaliero-Universitaria di Parma
Responsible party: Alessandra Dei Cas (Research Assistant, MD, PhD, Azienda Ospedaliero-Universitaria di Parma) — Principal investigator
First posted: Jul 28, 2016
Start date: Feb 2016
Primary completion: Jul 2019
Completion: Oct 31, 2021 (estimated)
Last update: Aug 17, 2021

Study contacts

Alessandra Dei Cas, MD

principal investigator · Azienda Ospedaliero-Universitaria di Parma

Oversight

Data monitoring committee: No

View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is status unknown, as verified in Aug 2021. You cannot join it, but the record below documents what was studied.

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