Deep Brain Stimulation for Human Morbid Obesity

NCT02232919 | Completed Phase 1 DMC

• 1 other identifier: 230/2012
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

The burden of morbid obesity to the circulatory, endocrine, and locomotor systems, as well as the psychological effects and related health-care costs, are well established in the medical literature. Lifestyle and dietary patterns remain critical factors modulating long-term weight control of morbidly obese individuals (bodymass index ≥ 40). Various dietary, pharmacological, and behavioral interventions have largely failed as therapies, often necessitating surgery as the last treatment option. Long term results of bariatric surgery suggest that sustained and substantial weight loss can decrease morbidity related to obesity secondary complications such as diabetes type 2 and cancers, enhancing the role of surgery for morbidly obese subjects. However the adverse effects of bariatric surgery are considerable and impact on quality of life. Its long-term failure rates and complications call for novel and effective long-term therapies, such as neurosurgical interventions. The investigators now propose to enhance our targeting capabilities in a feasibility study of low frequency electrical stimulation using VMH-DBS (ventromedial hypothalamic) in six morbidly obese patients. After successful targeting, DBS stimulation parameters will be systematically evaluated and individually optimized at three-month intervals over a one-year stimulation period. Detailed recording of side effects, weight changes, food intake patterns, metabolic changes, and behavioral evaluations will be obtained throughout the study.

Conditions

Obesity

Keywords

Deep Brain Stimulation

Outcome Measures

Primary Outcomes (1)

• Identification of possible adverse events related to stimulation of the VMH

  To identify potential side effects of continuous electrical stimulation of the VMH and optimize electrophysiological parameters to avoid these side effects in morbidly obese subjects.

  12 months

Secondary Outcomes (3)

• Body Weight

  12 months

• Body Composition

  12 months

• Food Intake.

  12 months

Study Arms (1)

Deep Brain Stimulation

EXPERIMENTAL

The design of this translation trial is a single-center, single cohort, open-label and non-masked study. The aim is to evaluate tolerability of chronic low-frequency electrical stimulation of the VMH, while achieving weight loss in morbidly obese subjects. The subjects must have a body-mass index \[BMI\] greater than 40, and no obesity co-morbidities, such as diabetes or cardiopulmonary abnormalities. Up to six subjects will be implanted in this protocol.

Device: Deep Brain Stimulation

Interventions

Deep Brain Stimulation DEVICE

If subjects qualify with respect to protocol requirements, the Medtronic Activa system will be implanted with the leads placed bilaterally in the VMH. Adjustment of DBS parameters at the three months visit will be performed to improve efficacy when the goal of 3% body weight loss mark was not achieved during this period of continuous stimulation. Subjects will be seen monthly after discharge throughout the study period. At visits, safety will be assessed through blood/urine tests, blood pressure measurements, verbal interviews with the subjects and family, quarterly formal psychiatric tests as well as QOL scales. The determination of efficacy will be the within-group percent change in weight at the end of the DBS treatment period compared to baseline.

Deep Brain Stimulation

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Body Mass Index \[BMI\] \>40 kg/m2. BMI definition = weight \[Kg\] / height \[m\]2
• Failed diet, exercise, behavior, and pharmacotherapy to control body weight.

You may not qualify if:

• Cancer requiring treatment in the past five years, with the exception of cancers which have been cured or, in the opinion of the investigator, carry a good prognosis \[for example, non melanoma skin cancer\].
• Infectious disease \[e.g., HIV or active tuberculosis\].
• Cardiovascular disease:
• i. Hospitalization for treatment of heart disease in the past 6 months. ii. New York Heart Association Functional Class \>2. iii. Left bundle branch block on EKG. iv. Third degree atrioventricular block on EKG. v. Uncontrolled hypertension \[average systolic blood pressure of \>160 mmHg or diastolic blood pressure \>95 mmHg on both screening visits\].
• vi. Pulse rate \>95 beats per minute on both screening visits. vii. Total serum cholesterol \>300 mg/dL. viii. Stroke or transient ischemic attack in the past 6 months.
• Gastrointestinal disease:
• i. Chronic hepatitis or cirrhosis. ii. Episode of alcoholic hepatitis or alcoholic pancreatitis. iii. Inflammatory bowel disease requiring treatment in the past year. iv. Recent or significant abdominal surgery \[e.g., gastrectomy or gastric bypass\].
• Renal disease:
• i. Serum creatinine \>1.5 mg/dL. ii. Urine protein\>2+ on dipstick at screening and or 24-hour urinary excretion of albumin\>500 mg/day.
• Lung disease:
• i. Chronic obstructive airway disease or asthma requiring daily therapy. ii. Use of home oxygen.
• Endocrine disease:
• i. Diabetes mellitus. ii. Hyperlipidemia with triacylglycerol \>500 mg/dL. iii. Hypothyroidism, hyperthyroidism. iv. Hypopituitarism. v. Hypogonadism.
• Psychological Disease:
• i. Major clinical depression. ii. Active psychiatric disorders. iii. Schizophrenia.

Sponsors & Collaborators

• Hospital do Coracao: lead

Study Sites (1)

Hospital do Coracao

São Paulo, São Paulo, 04005-000, Brazil

Location

Related Publications (1)

• De Salles AAF, Barbosa DAN, Fernandes F, Abucham J, Nazato DM, Oliveira JD, Cury A, Biasi A, Rossi R, Lasagno C, Bueno PT, Santos RHN, Damiani LP, Gorgulho AA. An Open-Label Clinical Trial of Hypothalamic Deep Brain Stimulation for Human Morbid Obesity: BLESS Study Protocol. Neurosurgery. 2018 Oct 1;83(4):800-809. doi: 10.1093/neuros/nyy024.

  PMID: 29538761 DERIVED

MeSH Terms

Conditions

Obesity

Interventions

Deep Brain Stimulation

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Surgical Procedures, Operative

Study Officials

• Alessandra Gorgulho, MD, MSc

  HOSPITAL DO CORAÇÃO

  STUDY CHAIR

• Antonio De Salles, M.D., Ph.D.

  HOSPITAL DO CORAÇÃO

  STUDY CHAIR

• Otavio Berwanger, MD,PhD

  HOSPITAL DO CORAÇÃO

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 21, 2014
• First Posted: September 5, 2014
• Study Start: April 1, 2014
• Primary Completion: April 1, 2016
• Study Completion: April 1, 2016
• Last Updated: September 29, 2016

Record last verified: 2016-09

Locations

BR (1)