Effects of Liraglutide on Hippocampal Structure and Function in Aging Adults With Prediabetes

NCT02140983 | Completed Phase 1 DMC

• 1 other identifier: 25076
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the effects of liraglutide on the memory and attention of people with insulin resistance. Liraglutide is a medication that makes the body more sensitive to insulin, and therefore may allow it to manage sugar more effectively. The investigators are looking specifically at a region of the brain that is associated with memory and attention, called the hippocampus, in order to see whether treatment this treatment will change performance on memory and attention tasks. The investigators are also taking an MRI of the brain to see whether there are changes to the size and shape of the hippocampus after treatment. All subjects in this study will be 50-70 years old and have pre- diabetes. Half of all subjects will have a family history of dementia, while the other half will not.

Conditions

Insulin Resistance; Dementia

Keywords

Insulin Resistance; Family History of Dementia; Cognition

Outcome Measures

Primary Outcomes (2)

• Cognitive Outcomes

  The following battery of tests will take approximately 90 minutes (at both baseline and 12-week follow-up) to complete and will be administered during the afternoon to avoid diurnal effects: Auditory Consonant Trigrams; Benton Visual Retention Test 5th Edition, Boston Naming Test, Buschke-Fuld Selective Reminding Test, Delis Kaplan Executive Function System (DKEFS), Color-Word subtest, DKEFS Tower Test, DKEFS Trail Making Test, DKEFS Verbal Fluency subtest, Purdue Pegboard, Rey-Osterrieth Complex Figure Test, Taylor Complex Figure Task, Wechsler Abbreviated Scale of Intelligence, and the Wechsler Adult Intelligence Scale-3rd Edition.

  Change from Baseline to 3 months

• OGTT

  Oral Glucose Tolerance Test (OGTT): After an overnight fast, subjects will be given a oral glucose challenge, wherein plasma glucose concentrations will be measured at baseline, T30min, T60min, T90min, and T120min after 75gm oral glucose load. Individuals with fasting glucose of 100-125 mg/dl and/or a 2-hour glucose of 140-199 mg/dL and less than 200 mg/dL will be eligible for study enrollment. OGTT will be repeated at the end of the study.

  Change from Baseline to 3 months

Study Arms (2)

Liraglutide

ACTIVE COMPARATOR

90 days of liraglutide treatment at adjusting dose, up to 1.8mg/day

Drug: Liraglutide

Placebo

PLACEBO COMPARATOR

90 days of placebo pen, up to 1.8mg/day.

Drug: Placebo

Interventions

Liraglutide DRUG

90 days of liraglutide up to 1.8mg/day.

Also known as: Victoza

Liraglutide

Placebo DRUG

Placebo medication

Placebo

Eligibility Criteria

• Age: 50 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects will be men and women between the ages of 50 and 70 yrs of age, with a BMI of 27 to 37 kg/m2 and at least 12 yrs of education.
• All subjects will be medically stable (i.e. no uncontrolled or poorly controlled medical illnesses), cognitively-intact as defined by Mini Mental Status Exam (MMSE) score of \> 27, and will have adequate visual and auditory acuity to allow for cognitive testing.
• Metabolic function will be determined as impaired fasting glucose 100-125 mg/dL and/or impaired 2-hr glucose concentration 140-199 and \<200mg/dL on 75-g oral glucose challenge.
• Also, half of all subjects will have a family history of dementia.

You may not qualify if:

• Diagnosis of possible or probable AD, MCI, or any other dementia; evidence of cognitive decline by MMSE score of \<27 or self-reported significant decline in memory within the past year (per the Memory Function Questionnaire) (MFQ)
• History of Type I or Type II diabetes, or fasting plasma glucose \> 126 mg/dL
• History of significant CVD or myocardial infarction; unstable cerebrovascular or pulmonary disease, gallstones, pancreatitis or cancer, multiple endocrine neoplasia (MEN) untreated hypothyroidism, unstable or untreated hypertension, anemia as determined by hematocrit \< 30%
• Abnormal renal clearance as determined by the serum creatinine ³ 1.5 mg/d, hepatic dysfunction as determined by ALT \> 2 times the upper limit of normal
• Presence of medications known to affect insulin action or insulin secretion
• Premature birth (which may affect MRI findings), history of neurological disorder (ischemic attacks, carotid bruits, or lacunes upon MRI scan), or evidence of neurologic or other physical illness that could produce cognitive deterioration; use of any drug that may significantly affect the OGTT results or cognitive testing results (specifically: cs)
• Drug or alcohol abuse or dependence within the past 6 months, positive urine toxicology screen for illicit substances at eligibility screening, history of mental illness, with the exception of past mood disorder, or evidence of acute depression as determined by a 17-item Hamilton Depression Rating Scale (HDRS-17) score of 8 or more.
• Participants with history of mood disorder must be in remission for at least 6 months prior to study entry.

Sponsors & Collaborators

• Stanford University: lead
• American Diabetes Association: collaborator

Study Sites (1)

Stanford Department of Psychiatry

Stanford, California, 94305, United States

Location

MeSH Terms

Conditions

Insulin Resistance; Dementia

Interventions

Liraglutide

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide 1; Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Natalie Rasgon, M.D., Ph.D.

  Stanford University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 27, 2014
• First Posted: May 16, 2014
• Study Start: August 1, 2013
• Primary Completion: February 1, 2017
• Study Completion: February 1, 2017
• Last Updated: January 25, 2018

Record last verified: 2018-01

Locations

US (1)