Galantamine Effects in Patients With Metabolic Syndrome (GALANTA-MS)

February 13, 2017 updated by: Fernanda Marciano Consolim- Colombo, University of Sao Paulo

Effects of Cholinergic Stimulation on Visceral Fat, Oxidative Stress and Inflammatory Markers in Patients With Metabolic Syndrome: a Randomized Clinical Trial

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.

Study Overview

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.

Study Type

Interventional

Enrollment (Actual)

60

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • São Paulo, Brazil, 05403-900
        • University of São Paulo, Heart Institute, Medical School

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 59 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Galantamine
  • 8 mg of Galantamine for 4 weeks
  • 16 mg Galantamine for 8 weeks
Oral use for 12 weeks
Other Names:
  • Reminyl ER
Placebo Comparator: Placebo
  • 8 mg of placebo for 4 weeks
  • 16 mg placebo for 8 weeks
Oral use for 12 weeks
Other Names:
  • Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Composite measure of cytokines and adipokines levels, to include IL-1, IL-6, TNF alpha, leptin and adiponectin
Time Frame: 12 weeks
12 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
Glucose, triglycerides and high density lipoprotein cholesterol levels
Time Frame: 12 weeks
12 weeks
Insulin levels
Time Frame: 12 weeks
12 weeks
Arterial blood pressure levels
Time Frame: 12 weeks
12 weeks
Heart Rate Variability
Time Frame: 12 weeks
12 weeks
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
12 weeks
Abdominal fat levels
Time Frame: 12 weeks
12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Fernanda M Consolim Colombo, Dra, University of Sao Paulo

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2014

Primary Completion (Actual)

March 1, 2015

Study Completion (Actual)

February 1, 2017

Study Registration Dates

First Submitted

October 7, 2014

First Submitted That Met QC Criteria

October 31, 2014

First Posted (Estimate)

November 5, 2014

Study Record Updates

Last Update Posted (Actual)

February 15, 2017

Last Update Submitted That Met QC Criteria

February 13, 2017

Last Verified

February 1, 2017

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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