Galantamine Effects in Patients With Metabolic Syndrome (GALANTA-MS)
Primary Purpose
Abdominal Obesity Metabolic Syndrome
Status
Completed
Phase
Phase 4
Locations
Brazil
Study Type
Interventional
Intervention
Galantamine
Placebo (for galantamine)
Sponsored by
About this trial
This is an interventional treatment trial for Abdominal Obesity Metabolic Syndrome focused on measuring Cholinergic Antagonists, Inflammation, Oxidative Stress
Eligibility Criteria
Inclusion:
Diagnosis of Metabolic Syndrome based on recently established criteria (three abnormal findings of the following five)
- Increased abdominal circumference ≥ 102 cm for men and 90 cm for women
- Low plasma level of HDL cholesterol < 40md/dL for men and 50 mg/dL for women
- Increased values for plasma triglycerides > 150 mg/dL
- Elevated blood pressure ≥130/85 mmHg
- Elevated level of blood sugar value to 100 mg/dL
- Body Mass Index (BMI) between 25 and 39, with weight maintenance diet and stable for at least 6 months before study entry
- Normal renal function and thyroid function
- Able to participate in the study by signing an informed consent form and comply with study stages throughout its duration
Exclusion:
- On use of antidiabetic medication
- Triglyceride levels ≥ 400 mg/dL or use of lipid lowering medication
- Levels of aspartate transaminase (AST) or alanine transaminase (ALT) ≥ 200 U/L
- Levels of aspartate transaminase (AST) or alanine transaminase (ALT) ≥ 200 U/L
- The office systemic blood pressure ≥160 mmHg or diastolic blood pressure ≥110 mmHg at rest
- BMI ≥ 40kg/m²
- In use of antihypertensive drugs that interfere with the heart rate variability
- On the use of drugs that have known or probable interaction with galantamine: amitriptyline, fluoxetine, fluvoxamine, ketoconazole, oxybutynin, paroxetine, quinidine
- Already participant in regular exercise programs, defined as 90 minutes of activity per week
- Medical history, previous diagnosis or previous supplementary examinations indicating presence of cardiac arrhythmias, coronary artery disease, valvular disease, heart failure, chronic obstructive pulmonary disease, acute or chronic liver disease, renal insufficiency, thyroid disorders, chronic inflammatory diseases, cancer, positive status for HIV, other debilitating diseases
- Abuse of alcohol or other substances in the 12 months prior to study entry
- History of major depression or patients with suicidal ideation
- Personal history of eating disorder
- Utilization of drugs for obesity
- Use of serotonin reuptake inhibitors
- Pregnancy or desire to become pregnant during the study period
Sites / Locations
- University of São Paulo, Heart Institute, Medical School
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Galantamine
Placebo
Arm Description
8 mg of Galantamine for 4 weeks 16 mg Galantamine for 8 weeks
8 mg of placebo for 4 weeks 16 mg placebo for 8 weeks
Outcomes
Primary Outcome Measures
Composite measure of cytokines and adipokines levels, to include IL-1, IL-6, TNF alpha, leptin and adiponectin
Secondary Outcome Measures
Glucose, triglycerides and high density lipoprotein cholesterol levels
Insulin levels
Arterial blood pressure levels
Heart Rate Variability
Composite measure of markers of oxidative stress, to include: total amount of free radicals, malondialdehyde, allantoin, anpha-1-antiproteinase, oxidize/reduced glutatione ratio
Abdominal fat levels
Full Information
NCT ID
NCT02283242
First Posted
October 7, 2014
Last Updated
February 13, 2017
Sponsor
University of Sao Paulo
Collaborators
University of Nove de Julho, Feinstein Institute for Medical Research
1. Study Identification
Unique Protocol Identification Number
NCT02283242
Brief Title
Galantamine Effects in Patients With Metabolic Syndrome
Acronym
GALANTA-MS
Official Title
Effects of Cholinergic Stimulation on Visceral Fat, Oxidative Stress and Inflammatory Markers in Patients With Metabolic Syndrome: a Randomized Clinical Trial
Study Type
Interventional
2. Study Status
Record Verification Date
February 2017
Overall Recruitment Status
Completed
Study Start Date
March 2014 (undefined)
Primary Completion Date
March 2015 (Actual)
Study Completion Date
February 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Sao Paulo
Collaborators
University of Nove de Julho, Feinstein Institute for Medical Research
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
It is recognized that inflammation can be modulated by cholinergic stimulation and that galantamine, an inhibitor of acetylcholinesterase enzyme with central nervous system action, has showed an anti-inflammatory effect, reducing body weight, abdominal fat and improvement in tissue insulin resistance in animal models. Galantamine is a safe drug that is used to treat alzheimer disease.Galantamine treatments of patients with the metabolic syndrome may represent a significant advance in management of this disease. This study aims to investigate the effects of galantamine on inflammatory markers, as well as on abdominal visceral and epicardial fat and oxidative stress in patients with metabolic syndrome. This is a pioneering study that will include expert support. The enrolling of subjects will have continuous monitoring throughout the period of treatment. The study is a double blind randomized prospective study with 60 patients with metabolic syndrome, to be randomized at ratio of 1: 1 placebo and galantamine. The dose of galanthamine is the standard clinically approved (8 and 16 mg). The tracking method include metabolic analysis, inflammatory and oxidative stress markers, hemodynamic evaluation with hear rate variability (sympatho vagal modulation) before, during and after treatment. Computerized tomography assessment of visceral abdominal and epicardial fat before and after treatment will be performed.
Detailed Description
Population: patients with metabolic syndrome; Intervention: Galantamine; Comparation: Placebo; Outcomes (primary): proinflammatory cytokines levels.
Description:
Patients with criteria of Metabolic Syndrome (with the 2005 revised NCEP ATP III criteria) will be randomized to 2 groups: use of galantamina (30 patients) or placebo (30 patients) in the following sequency:
I) 4 weeks of treatment with 8 mg of galantamine or placedo (oral ingestion capsules);
II) 8 weeks of treatment with 16 mg of galantamine or placebo (oral ingestion capsules).
Participants will receive a diary to record any symptoms that may present and will be instructed to bring it at each study visit.
Before randomization all participants will go through the following procedures:
Clinical and neurological evaluation;
Blood sample analysis of cytokines, oxidative stress and biochemical parameters;
Multidetector computed tomographic (MDCT) scan of abdomen (visceral - abdominal and epicardial fat) and thorax (calcium score);
blood pressure recording for hemodynamic evaluation and assessment of heart rate variability
24h ambulatory blood pressure measurement
These procedures will be repeated at the end of the protocol.
This is a randomized controlled trial study. Blinding status: Patients, investigators, and outcome assessors.
All participants were outpatients.
The invitation to participate in the study and all the details of the protocol will be explained.
Once the patients have the criteria for inclusion, they receive the cards with capsules containing placebo or galantamine according to continuous numerical order provided by the pharmacy that prepared and randomized such substances (numbered containers).
Drug and placebo will be manipulated and encapsulated in identical packaging at the Central Pharmacy of School of Medicine, University of São Paulo.
We will use simple randomisation using a randomisation table created by computer software - graphpad Software- quickcalcs.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Abdominal Obesity Metabolic Syndrome
Keywords
Cholinergic Antagonists, Inflammation, Oxidative Stress
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
60 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Galantamine
Arm Type
Experimental
Arm Description
8 mg of Galantamine for 4 weeks
16 mg Galantamine for 8 weeks
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
8 mg of placebo for 4 weeks
16 mg placebo for 8 weeks
Intervention Type
Drug
Intervention Name(s)
Galantamine
Other Intervention Name(s)
Reminyl ER
Intervention Description
Oral use for 12 weeks
Intervention Type
Drug
Intervention Name(s)
Placebo (for galantamine)
Other Intervention Name(s)
Placebo
Intervention Description
Oral use for 12 weeks
Primary Outcome Measure Information:
Title
Composite measure of cytokines and adipokines levels, to include IL-1, IL-6, TNF alpha, leptin and adiponectin
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Glucose, triglycerides and high density lipoprotein cholesterol levels
Time Frame
12 weeks
Title
Insulin levels
Time Frame
12 weeks
Title
Arterial blood pressure levels
Time Frame
12 weeks
Title
Heart Rate Variability
Time Frame
12 weeks
Title
Composite measure of markers of oxidative stress, to include: total amount of free radicals, malondialdehyde, allantoin, anpha-1-antiproteinase, oxidize/reduced glutatione ratio
Time Frame
12 weeks
Title
Abdominal fat levels
Time Frame
12 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
59 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion:
Diagnosis of Metabolic Syndrome based on recently established criteria (three abnormal findings of the following five)
Increased abdominal circumference ≥ 102 cm for men and 90 cm for women
Low plasma level of HDL cholesterol < 40md/dL for men and 50 mg/dL for women
Increased values for plasma triglycerides > 150 mg/dL
Elevated blood pressure ≥130/85 mmHg
Elevated level of blood sugar value to 100 mg/dL
Body Mass Index (BMI) between 25 and 39, with weight maintenance diet and stable for at least 6 months before study entry
Normal renal function and thyroid function
Able to participate in the study by signing an informed consent form and comply with study stages throughout its duration
Exclusion:
On use of antidiabetic medication
Triglyceride levels ≥ 400 mg/dL or use of lipid lowering medication
Levels of aspartate transaminase (AST) or alanine transaminase (ALT) ≥ 200 U/L
Levels of aspartate transaminase (AST) or alanine transaminase (ALT) ≥ 200 U/L
The office systemic blood pressure ≥160 mmHg or diastolic blood pressure ≥110 mmHg at rest
BMI ≥ 40kg/m²
In use of antihypertensive drugs that interfere with the heart rate variability
On the use of drugs that have known or probable interaction with galantamine: amitriptyline, fluoxetine, fluvoxamine, ketoconazole, oxybutynin, paroxetine, quinidine
Already participant in regular exercise programs, defined as 90 minutes of activity per week
Medical history, previous diagnosis or previous supplementary examinations indicating presence of cardiac arrhythmias, coronary artery disease, valvular disease, heart failure, chronic obstructive pulmonary disease, acute or chronic liver disease, renal insufficiency, thyroid disorders, chronic inflammatory diseases, cancer, positive status for HIV, other debilitating diseases
Abuse of alcohol or other substances in the 12 months prior to study entry
History of major depression or patients with suicidal ideation
Personal history of eating disorder
Utilization of drugs for obesity
Use of serotonin reuptake inhibitors
Pregnancy or desire to become pregnant during the study period
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Fernanda M Consolim Colombo, Dra
Organizational Affiliation
University of Sao Paulo
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of São Paulo, Heart Institute, Medical School
City
São Paulo
ZIP/Postal Code
05403-900
Country
Brazil
12. IPD Sharing Statement
Citations:
PubMed Identifier
28724799
Citation
Consolim-Colombo FM, Sangaleti CT, Costa FO, Morais TL, Lopes HF, Motta JM, Irigoyen MC, Bortoloto LA, Rochitte CE, Harris YT, Satapathy SK, Olofsson PS, Akerman M, Chavan SS, MacKay M, Barnaby DP, Lesser ML, Roth J, Tracey KJ, Pavlov VA. Galantamine alleviates inflammation and insulin resistance in patients with metabolic syndrome in a randomized trial. JCI Insight. 2017 Jul 20;2(14):e93340. doi: 10.1172/jci.insight.93340. eCollection 2017 Jul 20.
Results Reference
derived
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Galantamine Effects in Patients With Metabolic Syndrome
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