Primary Objective: To study the effect of VNS on BAT activity.Secondary Objective(s): Measure the effect of VNS on energy expenditure, core temperature, skin surface temperature and skin perfusion during active and absent stimulation.Follow the…
ID
Source
Brief title
Condition
- Appetite and general nutritional disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main endpoint of this study is BAT activity in kBq after active VNS.
Secondary outcome
Secondary endpoints are the effect of VNS on energy expenditure, body core
temperature, skin surface temperature, skin perfusion and food intake.
Other study parameters
Other relevant study parameters are medical history, medication, current
medical status, age, body weight, weight history, height, sex, thyroid gland
function, and UCP-1 and beta3-receptor polymorphisms.
Background summary
Obesity is reaching endemic proportions in our Western society. It is now
categorized as a chronic disease that is associated with severe comorbidities
as hypertension, type II diabetes and cancer. During the last decades research
in possible therapies for existing obesity and developmental factors causing
obesity has explosively increased. Recently renewed interest aroused in brown
adipose tissue (BAT), a tissue playing a possible role in both development and
therapy for obesity. BAT is active in adult man, but is decreased in activity
when body mass index (BMI) increases.
Many rodent studies report several active pathways for BAT activation, that is
highly innervated and vascularised. Stimulation of sympathetic beta-receptors
on BAT was already suggested to be a possible target for obesity several years
ago. Interestingly, stimulation of the cervical part of the vagus nerve (=
vagus nerve stimulation (VNS)) generates weight loss in rodents. Furthermore,
weight loss has been reported as a side-effect of VNS in humans, where it is
successfully to treat medically refractory epilepsy. Other studies show
effective weight loss applying a therapy that blocks the vagus nerve on the
abdominal level. Since the vagus nerve has both strong afferent and efferent
fibres, the vector of effect that induces weight loss is still unknown.
Moreover, the effect of blockage or stimulation of the vagus nerve rests on the
variation of the electrical pulse that has a certain amplitude and frequency.
Unfortunately, the level and characteristic of this pulse causing either
blockage or stimulation is not defined. The effect is only assumed to
hypothetically block or stimulate. Thus, the described blocking could be
stimulation and stimulation blockage. Nevertheless, this literature suggests
electric pulsing of the vagus nerve is accompanied by weight loss. Recent
studies report vagally mediated stimulation and suppression of BAT activity.
Increased BAT activity can increase energy expenditure and cause weight loss.
VNS and subsequent BAT activation could be a possible target in obesity. To
define the relation between BAT and VNS, we set up the following research
protocol. In this protocol BAT activity will be determined in subjects with
stable, completed VNS for epilepsy. We hypothesize that BAT activity increases
in VNS.
Study objective
Primary Objective:
To study the effect of VNS on BAT activity.
Secondary Objective(s):
Measure the effect of VNS on energy expenditure, core temperature, skin surface
temperature and skin perfusion during active and absent stimulation.
Follow the postoperative weight changes of the study population (this is a
retrospective objective)
UCP-1 and beta3-receptor polymorphisms.
Study design
In this study BAT activity is analyzed during active and absent VNS.
Measurements will be performed in a cohort of epilepsy patients that is already
treated with VNS. In these patients VNS consists of chronic cyclic electrical
stimulation of the left vagus nerve by a subcutaneously placed pulse generator
. The electrical pulses are transmitted by a helical bipolar electrode that is
connected to the vagus nerve . BAT activity can be accurately determined using
18-Fluoro-Deoxy-Glucose-Positron-Emission-Tomography-Computed-Tomograpy
(18-FDG-PET-CT or PET-imaging). In our group, previous results show good
determination of BAT localization and activity. In the Maastricht University
Medical Centre (MUMC) there is extensive experience with VNS for epilepsy since
1999. There is a postoperative cohort of epilepsy patients of approximately 200
patients in the Kempenhaeghe institute (Heeze, the Netherlands). Fifteen
patients from this cohort will be asked for two observational measurements.
Both measurements will be conducted at the department of nuclear medicine of
the MUMC. Before the first measurement a Dual-Energy-X-ray-Absorptiometry (DXA)
scan will be made to determine body composition. Randomized by a coin toss the
first measurement consists of PET-imaging with the VNS on or off. The second
measurement will be similar, but on another day to allow the effect of VNS to
fade out.
Addendum of mild cold exposure (version 5 of study protocol, September 2011):
To compare the effects of VNS on BAT with our previous studies that assessed
the effect of mild cold exposure on BAT, we will also measure the effects of
VNS on BAT under mild cold conditions. We will measure 5 subjects with active
VNS in both mild cold and thermoneutral conditions.
Intervention
In this study the VNS-system is switched off temporarily. This is not part of
the regular VNS treatment. Theoretically this could influence the frequency of
epileptic insults. On the other hand VNS is switched off frequently during
regular treatment during sports or public speaking. Therefore we do not expect
an increased risk of epileptic insults.
Study burden and risks
The absorbed radiation dose from the FDG PET-CT scan after administration of 74
MBq of 18F-FDG is 2.8 mSv. Subjects will be scanned twice, which is considered
as a low risk.
Postbus 616
6200 MD Maastricht
NL
Postbus 616
6200 MD Maastricht
NL
Listed location countries
Age
Inclusion criteria
Subjects treated with Vagus Nerve Stimulation (VNS) for epilepsy, aged 18-65 years, with a Body Mass Index (BMI) <= 28 kg/m2. Patients need to have optimally adjusted, stable VNS as judged by the treating neurologist.
Exclusion criteria
• Body Mass Index > 28 kg/m2
• Daily epileptic insults.
• Subjects that need or needed *Rapid Cycling* VNS to control their frequency of epileptic insults.
• Psychological unstable subjects (as judged by the treating neurologist).
• subjects with mental retardation (as judged by the treating neurologist).
• subjects with severe behaviour disorders (as judged by the treating neurologist).
• Pregnant subjects.
• Subjects that previously underwent high dose radiation for diagnostic or therapeutic purposes (radiotherapy, high frequency CT-scans).
• The use of the following medication is an exclusion criterium;
o ß-blockers,
o Ketogenic diet
• Subjects that recieved high doses of ionising radiation (x-ray or gamma radiation) in their medical history will be excluded.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL34114.068.10 |
| Other | www.clinicaltrials.gov, MEC 10-3-071, "Study of the effect of vagus nerve stimulation on human brown adipose tissue activity" |