NCT02847403

Brief 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).

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
40

participants targeted

Target at below P25 for phase_3

Timeline
Completed

Started Feb 2016

Longer than P75 for phase_3

Geographic Reach
1 country

2 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

February 1, 2016

Completed
6 months until next milestone

First Submitted

Initial submission to the registry

July 21, 2016

Completed
7 days until next milestone

First Posted

Study publicly available on registry

July 28, 2016

Completed
2.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2019

Completed
2.3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

October 31, 2021

Completed
Last Updated

August 17, 2021

Status Verified

August 1, 2021

Enrollment Period

3.4 years

First QC Date

July 21, 2016

Last Update Submit

August 10, 2021

Conditions

DysglycemiaCognitive Deficit

Keywords

dysglycemiaMCIexenatide LARGLP-1

Outcome Measures

Primary Outcomes (1)

  • 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.

    16 and 32 weeks

Secondary Outcomes (10)

  • Improvement of Mini Mental State Evaluation test at 16 (V2) and at 32 weeks (V3) compared to baseline

    16 and 32 weeks

  • Improvement of Mini Mental State Evaluation quality test at 16 (V2) and at 32 weeks (V3) compared to baseline

    16 and 32 weeks

  • Improvement of Phonemic verbal fluency test at 16 (V2) and at 32 weeks (V3) compared to baseline

    16 and 32 weeks

  • Improvement of Semantic verbal fluency test at 16 (V2) and at 32 weeks (V3) compared to baseline

    16 and 32 weeks

  • Improvement of Geriatric Depression Scale (GDS) test at 16 (V2) and at 32 weeks (V3) compared to baseline

    16 and 32 weeks

  • +5 more secondary outcomes

Study Arms (2)

exenatide

EXPERIMENTAL

long-acting exenatide 2 mg subcutaneously once-weekly

Drug: Exenatide

placebo

PLACEBO COMPARATOR

no drug assigned

Other: placebo

Interventions

ExenatideDRUG

Patients will be injected subcutaneously 2 mg long-acting exenatide once-weekly. No dose titration is foreseen.

Also known as: bydureon
exenatide
placeboOTHER

patients will be seen at the Center for Cognitive Disorders and Dementia according to their usual schedule.

placebo

Eligibility Criteria

Age51 Years - 79 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Endocrinology Unit

Parma, 43126, Italy

Location

Center for Cognitive Disorders and Dementia AUSL of Parma and University of Parma

Parma, Italy

Location

Related Publications (4)

  • 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.

    PMID: 17125767BACKGROUND

  • 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.

    PMID: 12925848BACKGROUND

  • 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.

    PMID: 23973293BACKGROUND

  • 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.

    PMID: 23728174BACKGROUND

MeSH Terms

Conditions

Cognition Disorders

Interventions

Exenatide

Condition Hierarchy (Ancestors)

Neurocognitive DisordersMental Disorders

Intervention Hierarchy (Ancestors)

PeptidesAmino Acids, Peptides, and ProteinsVenomsComplex MixturesToxins, BiologicalBiological Factors

Study Officials

  • Alessandra Dei Cas, MD

    Azienda Ospedaliero-Universitaria di Parma

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Research Assistant, MD, PhD

Study Record Dates

First Submitted

July 21, 2016

First Posted

July 28, 2016

Study Start

February 1, 2016

Primary Completion

July 1, 2019

Study Completion

October 31, 2021

Last Updated

August 17, 2021

Record last verified: 2021-08

Data Sharing

IPD Sharing
Will share

Locations

IT(2)