HIV Associated Cognitive Motor ComplexPhase 2CHINCT03384784
Effect of Galantamine on Inflammation and Cognition
A Phase 2 study testing Galantamine in people with HIV Associated Cognitive Motor Complex, run by University of Pennsylvania at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 30 years and older
- Conditions the study is for
- HIV Associated Cognitive Motor Complex
- What is being tested?
- Galantamine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 63 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Oct 2017to 31 May 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 30 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 18Show fewer
- 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
- Smoking Status
- Smokers (HIV+S) will report at least 5 instances of smoking per day, on average for the past year and provide a breath carbon monoxide (CO) sample greater than 5 ppm at Intake and at the beginning of each treatment period
- Non-smokers (HIV+NS) will report smoking fewer than 100 cigarettes in their lifetime, or less than 5 pack years of smoking and no cigarettes in the last year. They will self-report no current use of any tobacco or nicotine product and will provide a CO sample of less than 3 ppm at Intake and at the beginning of each treatment period. If CO sample does not reflect self-report, the PI will be consulted to determine eligibility.
Who cannot join
- 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
Show all 43Show fewer
- 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).
- Medical conditions contraindicated for use with galantamine:
- Diagnosis of Alzheimer's disease or dementia
- Epilepsy or other seizure disorder
- Bladder outflow obstruction
- Active HCV co-infection (if cured, requires study physician approval)
- Liver function tests more than 20% outside of the normal range; Gamma-glutamyl transpeptidase (GGT) values more than 20% outside of the normal range. If Albumin/Globulin ratios are 20% outside of normal range the abnormal value will be evaluated for clinical significance by the Study Physician and eligibility will determined on a case-by-case basis.
- Renal disease or renal dysfunction (e.g., serum creatinine levels greater than 1.5 X upper limit of normal). Those with moderate hepatic impairment or creatinine clearance 9 to 59 mL/min shall not exceed the 16 mg/day dose.
- Peptic ulcer disease (requires study physician approval)
- Suicide risk as indicated by at least one of the following on the Columbia Suicide Severity Rating Scale (the PI and/or study psychologist will be consulted to assess safety and determine eligibility in cases close to the eligibility cutoffs):
- Current suicidal ideation (within 30 days of enrollment)
- Two or more lifetime suicide attempts or episodes of suicidal behavior
- Any suicide attempt or suicidal behavior within 2 years of enrollment
- Medication
- Current use or discontinuation within the last 14 days of:
- Quit smoking medications including varenicline (Chantix), bupropion (Wellbutrin)
- Anti-psychotic medications (e.g., Zyprexa, Clozaril, Seroquel, Risperdal). If used to treat psychotic symptoms. Other uses may be eligible pending physician approval).
- Systemic Steroids (e.g., Prednisone).
- Alzheimer's disease medications (e.g., Acetylcholinesterase inhibitors (ACIs), Aricept/donepezil, Exelon/rivastigmine, Tacrine, or memantine)
- Irritable bowel syndrome medication (e.g., Dicyclomine/Bentyl)
- Heart medications (e.g., quinidine).
- Muscle relaxants (e.g., Anectine/succinylcholine)
- Anti-seizure medications (e.g. Ativan, Banzel, Carbatrol, Dilantin, Lamictal, Gabitril, Lyrica, Neurontin, Tegretol, Topomax) if used to treat a seizure disorder or epilepsy. Other uses may be eligible.
- Urinary retention medications (e.g., Duvoid/bethanechol, Proscar/finasteride, Avodart/dutasteride, Dibenzyline/ phenoxybenzamine, Regitine/phentolamine)
- Daily use of:
- Opiate-containing medications for chronic pain (Duragesic/fentanyl patches, Percocet, Oxycontin). Smokers who report taking opiate-containing medications on an "as-needed" basis will be instructed to refrain from use until their study participation is over and that they will be tested to ensure they have complied with this requirement.
- Chronic obstructive pulmonary disease (COPD) medication (e.g., Atrovent/Ipratropium Bromide)
- Known allergy to study medication.
- Subjects will be instructed to refrain from using any study prohibited drugs/medications (both recreational and prescription) throughout their participation in the study.
Trial locations and contacts
1 site in 1 country.
United States1 site
Center for Interdisciplinary Research on Nicotine Addiction, University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
Official title: Targeting the Cholinergic Pathway in HIV-associated Inflammation and Cognitive Dysfunction
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.
Read the detailed description
Although anti-retroviral therapy (ART) enhances life expectancy and overall quality of life (QoL), HIV-infected individuals are increasingly vulnerable to non-AIDS-related diseases including HIV-associated neurocognitive disorders (HAND). Inflammation is a primary mechanism in the pathogenesis of HAND and tobacco use may further exacerbate inflammation. Conversely, nicotine alone has anti-inflammatory effects suggesting that stimulating the cholinergic pathway via pharmacological treatment [e.g., galantamine (GAL)] may suppress inflammation and reverse or prevent neurocognitive deficits in HIV-1 infection. In this double-blind, placebo-controlled crossover study, HIV-infected individuals (N=120; 60 smokers, 60 nonsmokers) 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). All subjects will be stable on ART and the GAL dose will follow FDA guidelines. At the beginning and end of each treatment phase, inflammatory biomarkers and viral load will be assessed. Monocyte transcriptomics will also be assessed on a subset of the sample (n=60; 30/group). Neurocognition and clinical outcomes (e.g., QoL) will be measured at baseline and at 4-week intervals during each treatment phase. The primary outcomes are monocyte/macrophage and T-cell activation (CD16, CD163, and CC chemokine receptor type 2 or CCR2 expression; plasma CC chemokine ligand type 2 or CCL2 [MCP-1 or monocyte chemoattractant protein-1], sCD14; CD38/HLA-DR [cluster of differentiation 38/Human Leukocyte Antigen- antigen D Related] on CD8 [cluster of differentiation 8] cells) and neurocognitive performance (processing speed, verbal learning/memory, executive function). Exploratory outcomes include monocyte gene expression patterns and broad plasma cytokine analysis. This study will provide insight into the interactions among nAChR activation, HIV immune activation and pathogenesis, and tobacco use and has translational and therapeutic implications that could improve health outcomes among HIV-infected individuals.
- Conditions
- HIV Associated Cognitive Motor Complex
- Being tested
- Galantamine, Placebo
- Keywords
- HIV, Neurocognition, Inflammation, Galantamine, Nicotine, Tobacco Use
- Medical subject headings
- AIDS Dementia Complex, Inflammation, Tobacco Use
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GalantamineDrug
Also called Razadyne ER
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.
PlaceboDrug
Also called Sugar Pill
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Galantamine; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Period1 Lab 1 (Week 0), Period 1 Lab 2 (Week 12), Period 2 Lab 1 (Week 16), Period 2 Lab 2 (Week 28)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Dec 2017
- Study start30 Oct 2017
- Primary completion31 May 2022
- Study completion31 May 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HIV Associated Cognitive Motor ComplexStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 63 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Responsible party
- Sponsor
- Investigators
- Rebecca L Ashare, PhD, Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03384784
- Sponsor's protocol ID
- 828125
- Other IDs
- R01DA044906
- Acronym
- CHI
- Status last verified
- Oct 2024
- First submitted
- 8 Dec 2017
- Last updated
- 17 Oct 2024
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: The final dataset will include demographic and behavioral assessments and laboratory data bio-specimens. Because the dataset will contain personal health information, identifying information will be collected. Even though the final dataset will be stripped of identifiers prior to release for sharing, investigators will do the following to reduce the possibility confidentiality loss. We will make the data and associated documentation available to users only under a data-sharing agreement that provides for: (1) a commitment to using data only for research purposes and not to identify any individual participant; (2) a commitment to securing the data using appropriate computer technology; and (3) a commitment to destroying or returning the data after analyses are completed. Transcriptomic data will be deposited with a public access database such as NCBI's Gene Expression Omnibus (GEO) database (http://www.ncbi.nlm.nih.gov/geo/)
Study at a glance
From the registry record, last updated by the sponsor on 17 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Targeting the Cholinergic Pathway in HIV-associated Inflammation and Cognitive Dysfunction
- ClinicalTrials.gov ID
- NCT03384784
- Acronym / sponsor ID
- CHI / 828125
- Conditions
- HIV Associated Cognitive Motor Complex
- Keywords
- HIV, Neurocognition, Inflammation, Galantamine, Nicotine, Tobacco Use
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 63 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Study start
- 30 Oct 2017 (actual)
- Primary completion
- 31 May 2022 (actual)
- Study completion
- 31 May 2022 (actual)
- First posted
- 27 Dec 2017 (actual)
- Results
- Posted 17 Oct 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Although anti-retroviral therapy (ART) enhances life expectancy and overall quality of life (QoL), HIV-infected individuals are increasingly vulnerable to non-AIDS-related diseases including HIV-associated neurocognitive disorders (HAND). Inflammation is a primary mechanism in the pathogenesis of HAND and tobacco use may further exacerbate inflammation. Conversely, nicotine alone has anti-inflammatory effects suggesting that stimulating the cholinergic pathway via pharmacological treatment [e.g., galantamine (GAL)] may suppress inflammation and reverse or prevent neurocognitive deficits in HIV-1 infection. In this double-blind, placebo-controlled crossover study, HIV-infected individuals (N=120; 60 smokers, 60 nonsmokers) 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). All subjects will be stable on ART and the GAL dose will follow FDA guidelines. At the beginning and end of each treatment phase, inflammatory biomarkers and viral load will be assessed. Monocyte transcriptomics will also be assessed on a subset of the sample (n=60; 30/group). Neurocognition and clinical outcomes (e.g., QoL) will be measured at baseline and at 4-week intervals during each treatment phase. The primary outcomes are monocyte/macrophage and T-cell activation (CD16, CD163, and CC chemokine receptor type 2 or CCR2 expression; plasma CC chemokine ligand type 2 or CCL2 [MCP-1 or monocyte chemoattractant protein-1], sCD14; CD38/HLA-DR [cluster of differentiation 38/Human Leukocyte Antigen- antigen D Related] on CD8 [cluster of differentiation 8] cells) and neurocognitive performance (processing speed, verbal learning/memory, executive function). Exploratory outcomes include monocyte gene expression patterns and broad plasma cytokine analysis. This study will provide insight into the interactions among nAChR activation, HIV immune activation and pathogenesis, and tobacco use and has translational and therapeutic implications that could improve health outcomes among HIV-infected individuals.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Galantamine first | Experimental | Drug: Galantamine, Drug: PlaceboThis 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. |
| Placebo first | Placebo comparator | Drug: Galantamine, Drug: PlaceboThis 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. |
Who may qualify
- Ages
- 30 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- 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
Key exclusion criteria (43 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GalantamineAlso: Razadyne ERThe 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. | Drug | Galantamine first, Placebo first |
| PlaceboAlso: Sugar PillMatched 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. | Drug | Galantamine first, Placebo first |
Primary outcome
Change in Cognition
Time frame: Period1 Lab 1 (Week 0), Period 1 Lab 2 (Week 12), Period 2 Lab 1 (Week 16), Period 2 Lab 2 (Week 28)
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.
Change in Inflammation (MCP-1)
Time frame: Period1 Lab 1 (Week 0), Period 1 Lab 2 (Week 12), Period 2 Lab 1 (Week 16), Period 2 Lab 2 (Week 28)
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.
Change in Inflammation (Percentage of CD14+ Monocytes Expressing CD8)
Time frame: Period1 Lab 1 (Week 0), Period 1 Lab 2 (Week 12), Period 2 Lab 1 (Week 16), Period 2 Lab 2 (Week 28)
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.
Change in Inflammation (CD14)
Time frame: Period1 Lab 1 (Week 0), Period 1 Lab 2 (Week 12), Period 2 Lab 1 (Week 16), Period 2 Lab 2 (Week 28)
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.
Change in Inflammation (Percentage of CD14+ Monocytes Expressing CD163)
Time frame: Period1 Lab 1 (Week 0), Period 1 Lab 2 (Week 12), Period 2 Lab 1 (Week 16), Period 2 Lab 2 (Week 28)
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.
Change in Inflammation (Percentage of CD14+ Monocytes Expressing CD16)
Time frame: Period1 Lab 1 (Week 0), Period 1 Lab 2 (Week 12), Period 2 Lab 1 (Week 16), Period 2 Lab 2 (Week 28)
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Oct 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. The final dataset will include demographic and behavioral assessments and laboratory data bio-specimens. Because the dataset will contain personal health information, identifying information will be collected. Even though the final dataset will be stripped of identifiers prior to release for sharing, investigators will do the following to reduce the possibility confidentiality loss. We will make the data and associated documentation available to users only under a data-sharing agreement that provides for: (1) a commitment to using data only for research purposes and not to identify any individual participant; (2) a commitment to securing the data using appropriate computer technology; and (3) a commitment to destroying or returning the data after analyses are completed. Transcriptomic data will be deposited with a public access database such as NCBI's Gene Expression Omnibus (GEO) database (http://www.ncbi.nlm.nih.gov/geo/)
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rebecca L Ashare, PhD principal investigator
University of Pennsylvania
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Galantamine in people with HIV Associated Cognitive Motor Complex, run by University of Pennsylvania at 1 site in United States.
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 18 inclusion and 43 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: finished, as of the sponsor's last update on 17 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Oct 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Change in Cognition (time frame: Period1 Lab 1 (Week 0), Period 1 Lab 2 (Week 12), Period 2 Lab 1 (Week 16), Period 2 Lab 2 (Week 28)). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 Oct 2024.