Study of Liraglutide (A Weight Loss Drug) in High Risk Obese Participants With Cognitive and Memory Issues

Examining the Utility of GLP-1 Agonists as Neuroprotective Agents Through a Pilot Clinical Trial in High Risk Population With Neurocognitive Deficits and Obesity

This study is for people who have multiple sclerosis, acute leukemia (in remission), or long-COVID and a Body Mass Index over 27 and may struggle with cognitive issues such as remembering information, concentrating, or making decisions that affect everyday life.

By doing this study, researchers hope to learn how liraglutide (Saxenda®), a weight loss drug, affects levels of a certain disease marker in the body called Brain Derived Neurotrophic Factor (BDNF). Participation in this research will last about 21 weeks.

Study Overview

• Status: Not yet recruiting
• Conditions: Multiple Sclerosis; Obesity; Obesity, Morbid; Obese; Long COVID; Long Covid19; Acute Leukemia in Remission
• Intervention / Treatment: Drug: Liraglutide Pen Injector [Saxenda]; Other: Medication Diary

Detailed Description

This study is for people who have multiple sclerosis, acute leukemia (in remission), or long-COVID and a Body Mass Index over 27 and may struggle with cognitive issues such as remembering information, concentrating, or making decisions that affect everyday life. By doing this study, researchers hope to learn how liraglutide (Saxenda®), a weight loss drug, affects levels of a certain disease marker in the body called Brain Derived Neurotrophic Factor (BDNF).

Previous research has shown that liraglutide may help regulate BDNF levels, which can be linked to issues with cognitive and mental performance. Participation in this research will last about 21 weeks.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Adam DuVall, MD; Phone Number: (773) 702-8951; Email: duvalla@medicine.bsd.uchicago.edu
• Study Contact Backup: Name: Anthony Reder, MD; Phone Number: 773-702-6222; Email: cancerclinicaltrials@bsd.uchicago.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients with MS, acute leukemia in remission, or long-COVID and subjective symptoms of cognitive impairment a. Patients with acute leukemia must be in remission for at least 6 months but may be on maintenance therapy

   • Must have BMI greater than or equal to 27 along with one weight related condition such as hypertension, insulin resistance, or dyslipidemia or with BMI greater than or equal to 30 alone
   • Ages ≥18 but <40 years old

   • Adequate organ function as defined by the following:

     1. Creatinine ≤1.5 mg/dL
     2. Aspartate aminotransferase (AST) and alanine transaminase (ALT) ≤5 x upper limit normal (ULN) and bilirubin ≤1.5 mg/dL
   • Participants must be at least 2 months from major surgery, radiation therapy, or participation in other investigational trials, and must have recovered from clinically significant toxicities related to these prior treatments.
   • Female participants of childbearing potential must have negative results for a pregnancy test at baseline testing time point
   • Must be willing to use appropriate contraception
   • The effects of liraglutide on the developing human fetus are unknown. For this reason, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 8 weeks after completion of liraglutide administration.
   • Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

• History of multiple endocrine neoplasia type 2 (MEN2)
• Personal or family history of thyroid cancer
• Previous or current diagnosis of acute and/or chronic pancreatitis
• Any prior GLP-1 agonist therapy
• Poorly controlled diabetes mellitus with an indication for liraglutide (Victoza) for its management
• Previous or current diagnosis of fibromyalgia
• Participants who are receiving any other investigational agents.
• Participants with a "currently active" second malignancy other than non-melanoma skin cancers. Patients are not considered to have a "currently active" malignancy if they have completed therapy and are free of disease for ≥ 3 years.
• Participants with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to liraglutide.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant women are excluded from this study because liraglutide is a Category X agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with liraglutide, breastfeeding should be discontinued prior to enrollment in the trial.
• Participants with congenital cognitive dysfunction or severe cognitive dysfunction unrelated to diagnosis of leukemia, Multiple Sclerosis, or COVID.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Study Group 1 (Drug Regimen A); During the study, liraglutide will be given in "cycles." A cycle is a scheduled period of time for taking study drugs. For this study, each cycle length as well as the dose of liraglutide participants take will be based on the drug regimen (or schedule) they receive. The drug regimen receive each participant receives will be selected using a random assignment process, similar to flipping a coin. Participants in this study group will receive Drug Regimen A, which means they will take liraglutide at the below doses and times: Dose Schedule Cycle Length 0.6mg Daily 1 week 1.2mg Daily 1 week 1.8mg Daily 1 week 2.4mg Daily 1 week 3.0mg Daily 8 weeks	Drug: Liraglutide Pen Injector [Saxenda]; A weight loss drug that can be taken at home. Liraglutide will be provided as an injectable pen that participants can inject in the stomach, thigh or upper arm. A member of the research team will give you instructions on how to inject liraglutide using the injectable pen and answer any questions.; Other Names: Victoza; Saxenda; Other: Medication Diary; Participants will be asked to maintain a medication diary of each dose of liraglutide. A member of the research team will provide a copy of this diary for participants to complete. Participants will be asked to return this medication diary to research staff at each clinic visit.
Experimental: Study Group 2 (Drug Regimen B); During the study, liraglutide will be given in "cycles." A cycle is a scheduled period of time for taking study drugs. For this study, each cycle length as well as the dose of liraglutide participants take will be based on the drug regimen (or schedule) they receive. The drug regimen receive each participant receives will be selected using a random assignment process, similar to flipping a coin. Participants in this study group will receive Drug Regimen B, which means they will take liraglutide at the below doses and times: Dose Schedule Cycle Length 0.6mg Daily 5 weeks 1.2mg Daily 1 week 1.8mg Daily 1 week 2.4mg Daily 1 week 3.0mg Daily 4 weeks	Drug: Liraglutide Pen Injector [Saxenda]; A weight loss drug that can be taken at home. Liraglutide will be provided as an injectable pen that participants can inject in the stomach, thigh or upper arm. A member of the research team will give you instructions on how to inject liraglutide using the injectable pen and answer any questions.; Other Names: Victoza; Saxenda; Other: Medication Diary; Participants will be asked to maintain a medication diary of each dose of liraglutide. A member of the research team will provide a copy of this diary for participants to complete. Participants will be asked to return this medication diary to research staff at each clinic visit.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in Serum Brain Derived Neurotrophic Factor (BDNF) after 8 Weeks	Change from baseline in serum Brain Derived Neurotrophic Factor (BDNF) levels after reaching the goal dose of GLP-1 agonist (8 weeks).	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in Serum Brain Derived Neurotrophic Factor (BDNF) after 4 Weeks	Change from baseline in serum Brain Derived Neurotrophic Factor (BDNF) levels at 4 weeks.	4 weeks
Change from Baseline in Serum Brain Derived Neurotrophic Factor (BDNF) after 12 Weeks	Change from baseline in serum Brain Derived Neurotrophic Factor (BDNF) levels at 12 weeks.	12 weeks
Change from Baseline in Serum Brain Derived Neurotrophic Factor (BDNF) after 21 Weeks	Change from baseline in serum Brain Derived Neurotrophic Factor (BDNF) levels at discontinuation of study drug (21 weeks).	21 weeks

Collaborators and Investigators

• Sponsor: University of Chicago
• Investigators: Principal Investigator: Adam DuVall, MD, University of Chicago Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): October 1, 2026

Study Registration Dates

• First Submitted: December 6, 2023
• First Submitted That Met QC Criteria: December 6, 2023
• First Posted (Actual): December 14, 2023

Study Record Updates

• Last Update Posted (Estimated): December 27, 2023
• Last Update Submitted That Met QC Criteria: December 19, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Disease Attributes; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Chronic Disease; Post-Infectious Disorders; COVID-19; Multiple Sclerosis; Obesity; Obesity, Morbid; Post-Acute COVID-19 Syndrome; Hypoglycemic Agents; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Incretins; Liraglutide
• Other Study ID Numbers: IRB23-0848

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No