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DysglycemiaPhase 3DRINNNCT02847403

Long-acting Exenatide and Cognitive Decline in Dysglycemic Patients

A Phase 3 study testing Exenatide in people with Dysglycemia and Cognitive Deficit, run by Azienda Ospedaliero-Universitaria di Parma at 2 sites in Italy.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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 more about this study

Who is it for?
Ages 51 to 79 years
Conditions the study is for
Dysglycemia, Cognitive Deficit
What is being tested?
Exenatide
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
40 participants
Where
2 sitesItaly
Study dates
Feb 2016to 31 Oct 2021
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 51 to 79 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 15Show fewer
  • 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.

Trial locations and contacts

2 sites in 1 country.

Italy2 sites

  • Endocrinology Unit

    Parma, 43126

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

    Parma

Other trials in Italy

About this study

Official title: 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).

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.

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).
Being tested
Exenatide, placebo
Keywords
dysglycemia, MCI, exenatide LAR, GLP-1
Medical subject headings
Cognition Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ExenatideDrug

    Also called bydureon

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

  • placeboOther

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

Study groups in NCT02847403
Study groupRoleWhat they receive
exenatideExperimentallong-acting exenatide 2 mg subcutaneously once-weekly
Receives: Drug: Exenatide
placeboPlacebo comparatorno drug assigned
Receives: Other: placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 16 and 32 weeks

Secondary outcomes (10)

  1. 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.

    Measured: 16 and 32 weeks

  2. 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.

    Measured: 16 and 32 weeks

  3. 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.

    Measured: 16 and 32 weeks

  4. 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.

    Measured: 16 and 32 weeks

  5. 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.

    Measured: 16 and 32 weeks

  6. 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.

    Measured: 16 and 32 weeks

  7. 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.

    Measured: 16 and 32 weeks

  8. 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.

    Measured: 16 and 32 weeks

  9. 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.

    Measured: 16 and 32 weeks

  10. 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

    Measured: 16 and 32 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Jul 2016 (estimated)
  2. Study startFeb 2016
  3. Primary completionJul 2019
  4. Study completion31 Oct 2021 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
40 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02847403
Sponsor's protocol ID
2015-001850-13
Other IDs
2015
Acronym
DRINN
Status last verified
Aug 2021
First submitted
21 Jul 2016
Last updated
17 Aug 2021
Results posted
No
Data monitoring committee
No
Individual data sharing
Yes

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

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Exenatide in people with Dysglycemia and Cognitive Deficit, run by Azienda Ospedaliero-Universitaria di Parma at 2 sites in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 17 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02847403, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Aug 2021.

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