Effect of Galantamine on Inflammation and Cognition

NCT03384784 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 828125R01DA044906
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 1

Brief Summary

This study tests whether galantamine (GAL) reduces HIV-related inflammation and cognitive deficits. In this double-blind placebo-controlled crossover study, HIV-infected individuals (N=120; 60 smokers and 60 non-smokers) will be randomized to 12 weeks of GAL or placebo, followed by a 4-week washout, then 12 weeks of GAL or placebo (arms switched). Outcomes are monocyte/macrophage and T cell activation and neurocognitive performance.

Conditions

HIV Associated Cognitive Motor Complex

Keywords

HIV; Neurocognition; Inflammation; Galantamine; Nicotine; Tobacco Use

Outcome Measures

Primary Outcomes (6)

• Change in Cognition

  Cognitive function will be assessed 4 times at Lab Visits. Executive function was measured by the task switch cost from the Color shape task, measured in ms. Executive function was also measured via response time (ms) and accuracy (# correct) on an N-back working memory task. Verbal learning and memory were measured by the Total Recall and Delayed Recall, respectively, from the Hopkins Verbal Learning Test. Response inhibition was measured by the stop signal reaction time (ms) from the Stop Signal Task. A composite score will be created by computed standardized z-scores for each measure (where the mean is 0 and the standard deviation is 1) and then averaging the z-scores. Measures of response time were reverse coded such that higher z-scores indicate better cognitive performance. The primary outcome is the change from baseline cognitive function after 12 weeks of treatment. Change in cognition will be measured during each treatment arm.

  Period1 Lab 1 (Week 0), Period 1 Lab 2 (Week 12), Period 2 Lab 1 (Week 16), Period 2 Lab 2 (Week 28)

• Change in Inflammation (MCP-1)

  Cellular markers of immune activation will be measured in whole blood and soluble markers of immune activation will be measured in plasma at Lab Visits. The primary outcome is the change in monocyte and T cell surface activation and soluble markers after 12 weeks of treatment. Because this is a within-subject crossover study, changes in cellular markers will be measured during each treatment arm.

  Period1 Lab 1 (Week 0), Period 1 Lab 2 (Week 12), Period 2 Lab 1 (Week 16), Period 2 Lab 2 (Week 28)

• Change in Inflammation (Percentage of CD14+ Monocytes Expressing CD8)

  Cellular markers of immune activation will be measured in whole blood and soluble markers of immune activation will be measured in plasma at Lab Visits. The primary outcome is the change in monocyte and T cell surface activation and soluble markers after 12 weeks of treatment. Because this is a within-subject crossover study, changes in cellular markers will be measured during each treatment arm.

  Period1 Lab 1 (Week 0), Period 1 Lab 2 (Week 12), Period 2 Lab 1 (Week 16), Period 2 Lab 2 (Week 28)

• Change in Inflammation (CD14)

  Cellular markers of immune activation will be measured in whole blood and soluble markers of immune activation will be measured in plasma at Lab Visits. The primary outcome is the change in monocyte and T cell surface activation and soluble markers after 12 weeks of treatment. Because this is a within-subject crossover study, changes in cellular markers will be measured during each treatment arm.

  Period1 Lab 1 (Week 0), Period 1 Lab 2 (Week 12), Period 2 Lab 1 (Week 16), Period 2 Lab 2 (Week 28)

• Change in Inflammation (Percentage of CD14+ Monocytes Expressing CD163)

  Cellular markers of immune activation will be measured in whole blood and soluble markers of immune activation will be measured in plasma at Lab Visits. The primary outcome is the change in monocyte and T cell surface activation and soluble markers after 12 weeks of treatment. Because this is a within-subject crossover study, changes in cellular markers will be measured during each treatment arm.

  Period1 Lab 1 (Week 0), Period 1 Lab 2 (Week 12), Period 2 Lab 1 (Week 16), Period 2 Lab 2 (Week 28)

• Change in Inflammation (Percentage of CD14+ Monocytes Expressing CD16)

  Cellular markers of immune activation will be measured in whole blood and soluble markers of immune activation will be measured in plasma at Lab Visits. The primary outcome is the change in monocyte and T cell surface activation and soluble markers after 12 weeks of treatment. Because this is a within-subject crossover study, changes in cellular markers will be measured during each treatment arm.

  Period1 Lab 1 (Week 0), Period 1 Lab 2 (Week 12), Period 2 Lab 1 (Week 16), Period 2 Lab 2 (Week 28)

Study Arms (2)

Galantamine first

EXPERIMENTAL

This is a crossover study such that all participants receive both placebo and galantamine. Participants were randomized to receive galantamine first and placebo second. Timepoints Week 0 through Week 12 represent the first period and Weeks 16 through 28 represent the second period. This study follows the FDA-recommended dosing regimen for galantamine extended release (GAL ER): 4 weeks at 8 mg (once a day), 4 weeks at 16 mg (once a day), and 4 weeks at 24 mg (once a day). The University of Pennsylvania Investigational Drug Service (IDS) will oversee the randomization of all study medication, purchase study medication, manufacture matched placebo, encapsulate and package them in blister packs to maintain double-blind procedures.

Drug: Galantamine; Drug: Placebo

Placebo first

PLACEBO COMPARATOR

This is a crossover study such that all participants receive both placebo and galantamine. Participants were randomized to receive galantamine first and placebo second. Timepoints Week 0 through Week 12 represent the first period and Weeks 16 through 28 represent the second period. Placebo ingredients will be purchased, encapsulated, and packaged into blister packs by the IDS at the University of Pennsylvania. Both active medication and placebo will look identical. The study medication assignments for each participant in this project is randomized and counterbalanced. This means that approximately 50% of participants will take galantamine during the first medication period, followed by the placebo in the second medication period. Alternatively, approximately 50% of participants will take the placebo during the first medication period, followed by galantamine during the second medication period.

Drug: Galantamine; Drug: Placebo

Interventions

Galantamine DRUG

The study will be performed using the 8mg, 16mg and 24mg doses of galantamine hydrobromide-ER. The dosing regimen will be an initial 4 weeks of drug run-up at the lowest 8mg q.d. dose, followed by 16mg q.d. for the following 4 weeks, and the dose will be increased for the last 4 weeks to 24mg. Participants will be instructed to take one 8mg 16mg or 24mg pill (galantamine-ER or placebo) every morning, preferably with food.

Also known as: Razadyne ER

Galantamine first; Placebo first

Placebo DRUG

Matched placebo will be made in-house using lactulose filler in gel capsules. Participants will be instructed to take one pills every morning for 12 weeks.

Also known as: Sugar Pill

Galantamine first; Placebo first

Eligibility Criteria

• Age: 30 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Eligible subjects will be males and females:
• At least 30 years old
• Diagnosed with HIV-1 infection
• On stable ART regimens (no changes to treatment within 4 weeks of Intake visit)
• Viral load of less than or equal to 200 copies/mL
• Current cluster of differentiation (CD4) counts greater than 200
• If current or past diagnosis of bipolar disorder, eligible if:
• No psychotic features
• Montgomery-Asberg Depression Rating Scale (MADRS): total score less than 8 (past 4 weeks), suicidal item score less than 1 (past 4 weeks)
• Young Mania Rating Scale (Y-MRS): total score less than 8 (past 4 weeks), irritability, speech content, disruptive or aggressive behavior items score less than 3 (past 4 weeks)
• No psychiatric hospitalization or Emergency Room visits for psychiatric issues in the past 6 months
• No aggressive or violent acts or behavior in the past 6 months
• Able to communicate in English and provide written informed consent
• Will be residing in the geographic area for at least 7 months
• Not currently trying to quit smoking

You may not qualify if:

• Subjects who present with and/or self-report the following criteria will not be eligible to participate in the study.
• Smoking Behavior
• Current enrollment or plans to enroll in another smoking cessation program in the next 7 months.
• Regular (daily) use of electronic cigarettes, chewing tobacco, snuff, snus, cigars, cigarillos, or pipes.
• Current use or plans to use nicotine substitutes (gum, patch, lozenge, e-cigarette) or smoking cessation treatments in the next 7 months.
• Alcohol/Drug Use
• Current untreated and unstable diagnosis of substance abuse or dependence (if past use and if receiving treatment and stable for at least 30 days, eligible)
• Positive urine drug screen for cocaine, methamphetamines, phencyclidine (PCP), barbiturates, ecstasy (MDMA), at Intake or Lab visits. Those who screen positive for amphetamines, benzodiazepines, methadone, oxycodone, and/or opiates (low level cut-off 300 ng/mL) and who are prescribed these medications will be reviewed on a case-by-case basis by the study physician and PIs (see Measures and Table 1 for details). Participants believed to have a false-positive result on the drug screen may continue in the study, with investigator approval.
• Medical/Psychiatric Conditions
• Women who are pregnant, planning a pregnancy or lactating
• Current diagnosis of unstable and untreated major depression (if stable for at least 30 days, eligible)
• Current or past diagnosis of psychotic disorder
• Cancer diagnosis within the past 6 months (except basal cell carcinoma)
• Major heart disease or stroke within the past 6 months
• Uncontrolled hypertension (systolic blood pressure greater than 160 or diastolic blood pressure greater than 100).

Sponsors & Collaborators

• University of Pennsylvania: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Center for Interdisciplinary Research on Nicotine Addiction, University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

AIDS Dementia Complex; Inflammation; Tobacco Use

Interventions

Galantamine; Sugars

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Neurocognitive Disorders; Mental Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Amaryllidaceae Alkaloids; Alkaloids; Heterocyclic Compounds; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Carbohydrates

Results Point of Contact

• Title: Rebecca Ashare
• Organization: University of Pennsylvania

rlashare@pennmedicine.upenn.edu

215.746.7143

Study Officials

• Rebecca L Ashare, PhD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 8, 2017
• First Posted: December 27, 2017
• Study Start: October 30, 2017
• Primary Completion: May 31, 2022
• Study Completion: May 31, 2022
• Last Updated: October 17, 2024
• Results First Posted: October 17, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data will be made available starting 6 months after the summary data are published or January 2024 (whichever comes first) and will be made available for 5 years.
• Access Criteria: The PIs will review requests for data and all users must sign a data sharing agreement as described above.

Locations

US (1)