Galantamine Effects in Patients With Metabolic Syndrome

NCT02283242 | Completed Phase 4 DMC

• 2 other identifiers: CAAE:27386114.9.0000.00682013/22250-9
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Abdominal Obesity Metabolic Syndrome

Keywords

Cholinergic Antagonists; Inflammation; Oxidative Stress

Outcome Measures

Primary Outcomes (1)

• Composite measure of cytokines and adipokines levels, to include IL-1, IL-6, TNF alpha, leptin and adiponectin

  12 weeks

Secondary Outcomes (6)

• Glucose, triglycerides and high density lipoprotein cholesterol levels

  12 weeks

• Insulin levels

  12 weeks

• Arterial blood pressure levels

  12 weeks

• Heart Rate Variability

  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

  12 weeks

Study Arms (2)

Galantamine

EXPERIMENTAL

* 8 mg of Galantamine for 4 weeks * 16 mg Galantamine for 8 weeks

Drug: Galantamine

Placebo

PLACEBO COMPARATOR

* 8 mg of placebo for 4 weeks * 16 mg placebo for 8 weeks

Drug: Placebo (for galantamine)

Interventions

Galantamine DRUG

Oral use for 12 weeks

Also known as: Reminyl ER

Galantamine

Placebo (for galantamine) DRUG

Oral use for 12 weeks

Also known as: Placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 59 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Sao Paulo: lead
• University of Nove de Julho: collaborator
• Feinstein Institute for Medical Research: collaborator

Study Sites (1)

University of São Paulo, Heart Institute, Medical School

São Paulo, São Paulo, 05403-900, Brazil

Location

Related Publications (1)

• 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.

  PMID: 28724799 DERIVED

MeSH Terms

Conditions

Abdominal obesity metabolic syndrome; Inflammation

Interventions

Galantamine

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

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

Study Officials

• Fernanda M Consolim Colombo, Dra

  University of Sao Paulo

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Fernanda Marciano Consolim Colombo, MD, PhD

Study Record Dates

• First Submitted: October 7, 2014
• First Posted: November 5, 2014
• Study Start: March 1, 2014
• Primary Completion: March 1, 2015
• Study Completion: February 1, 2017
• Last Updated: February 15, 2017

Record last verified: 2017-02

Locations

BR (1)