Liraglutide for HIV-associated Neurocognitive Disorder

Study Overview
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Brief Summary
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This study will test the effect of liraglutide on cognitive function in HIV-infected overweight or obese subjects with type 2 diabetes.

Detailed Description
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HIV, insulin resistance and type 2 diabetes mellitus (DM) are independently associated with cognitive impairment. Considering the synergistic effects of HIV and DM on cognition, these subjects are at increased risk of cognitive impairment. glucagon-like peptide 1 (GLP-1) receptors have wide tissue distribution including the central nervous system. The study hypothesis is that GLP-1 could potentially ameliorate the impairments in cognition in this population. This study will assess the impact of liraglutide on neurocognitive performance and peripheral inflammatory markers. It will also evaluate the effects of liraglutide on glycemic control and metabolic risk factors in HIV infected subjects with type 2 diabetes.

Official Title
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Effects of Liraglutide on Cognition, Chronic Inflammation and Glycemic Control in Overweight and Obese, HIV-infected Subjects With Type 2 Diabetes.

Conditions
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HIV Infection, Diabetes Mellitus Type 2, Obesity, Overweight, Metabolic Syndrome

Intervention / Treatment
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* Drug: Liraglutide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV controlled on therapy for at least 12 weeks Viral load < 200 copies BMI >27 to 45 Diagnosis of DM type 2 with A1-C >7 to 15 Participants must be willing to comply with all study related procedures Exclusion Criteria: Personal or family history of pancreatitis Medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia Syndrome Type 2 (MEN 2) Gastroparesis Allergy to liraglutide or any of the active ingredients in liraglutide or other GLP-1 analogue Weight loss drugs other than metformin Type 1 diabetes mellitus or diabetic ketoacidosis Known major cognitive deficit dementia, history of head trauma with loss of consciousness >30 min, history of stroke, current central nervous system (CNS) disorder such as seizures or opportunistic CNS infection Renal insufficiency defined as creatinine clearance < 60 mL/min Active opportunistic infections Pregnancy or breastfeeding Unstable cardiovascular disease with hospitalization within 1 year for acute coronary syndrome Decompensated heart failure Substance abuse Active alcohol or opioid substitution therapy Serious or unstable medical or psychological conditions that would compromise the subject's safety for successful participation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Liraglutide<br> | Drug: Liraglutide<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neurocognitive performance- change in global cognitive scores on a standard neuropsychological profile |  | 6 months | 
| Neurocognitive performance- change in domain averages on a standard neuropsychological profile |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline high sensitivity C-reactive protein |  | 3 and 6 months | 
| Change from baseline d-dimer |  | 3 and 6 months | 
| Change from baseline Interleukin 6 |  | 3 and 6 months | 
| Change from baseline plasma soluble cluster of differentiation 14 (CD14) |  | 3 and 6 months | 
| Change from baseline BMI |  | 3 and 6 months | 
| Change from baseline weight |  | 3 and 6 months | 
| Change from baseline waist circumference |  | 3 and 6 months | 
| Change from baseline blood pressure |  | 3 and 6 months | 
| Change from baseline serum triglycerides |  | 3 and 6 months | 
| Change from baseline insulin resistance by homeostasis model assessment (HOMA-IR) in subjects not on insulin |  | 3 and 6 months | 
| Change from baseline liver enzymes aspartate aminotransferase and alanine aminotransferase |  | 3 and 6 months | 
| Change from baseline Hemoglobin A1c |  | 3 and 6 months | 
| Change from baseline fructosamine |  | 3 and 6 months | 
| Number of Adverse events |  | 3 and 6 months | 
| Number of subjects with Adverse events |  | 3 and 6 months | 
| Change from baseline serum LDL |  | 3 and 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV infection, Diabetes Mellitus type 2, Obesity, Neurocognitive function