To study the effects of post-ingestion nutrients on brain activity and brain dopaminergic responses in lean subjects, and in obese subjects before and after diet-induced weight loss.
ID
Source
Brief title
Condition
- Appetite and general nutritional disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The effect of intragastric infusion of nutrients on:
- Brain activity assessed as the induced change in BOLD signal and resting
state brain connectivity measured with fMRI.
- Striatal dopamine response, measured as the change in D2/D3R binding
potential of IBZM assessed by SPECT.
Secondary outcome
The effect of intragastric infusion of nutrients on:
- Glucoregulatory and gut hormone release
- Objective scores of hunger and satiety during a buffet test meal after the
infusion of the nutrients.
- Subjective (VAS) scores of hunger and satiety
- Neuropsychological functioning and feeding behaviour characteristics assessed
by questionnaires and tasks
Assess the correlations between brain activity and weight loss maintenance one
year after the diet intervention
Background summary
The worldwide obesity epidemic is a major health burden. Obesity is caused by
disturbed feeding behaviour, leading to overconsumption of high-calorie and
highly palatable food. Feeding behaviour is regulated by a complex interplay of
the homeostatic and hedonic systems, and influenced by peripheral inputs.
Recent evidence suggests that ingested nutrients trigger gut-to-brain signals
that stimulate central (brain) dopamine release. Changes in post-ingestion
nutrient signals may be involved in the development of the pathological
(habitual/compulsive) feeding behaviour in obese humans. However, the mechanism
of nutrient-triggered dopamine release and its potential role in obesity remain
to be elucidated. Gaining more insight in post-ingestion nutrient signalling is
necessary to develop new therapeutic options to restore disturbed feeding
behaviour in obesity.
Study objective
To study the effects of post-ingestion nutrients on brain activity and brain
dopaminergic responses in lean subjects, and in obese subjects before and after
diet-induced weight loss.
Study design
Single-blind randomized cross-over study
Intervention
Intragastric infusion of nutrients
Study burden and risks
Lean subjects will visit the AMC on 6 occasions (1 training, 3 fMRI, 2 SPECT
sessions). Obese subjects will visit the AMC on 5 occasions at baseline (1
training, 3 fMRI, 1 SPECT sessions), and on 4 occasions after a 3-month dietary
weight loss intervention (3 fMRI, 1 SPECT session) and on one occasion 1 year
after the diet intervention to assess weight loss maintenance. The diet
intervention is designed to result in ~10% body weight loss. The effect of the
intragastric infusion of nutrients on BOLD will be assessed by fMRI, which is a
non-invasive imaging modality. The effect of intragastric nutrient infusion on
striatal D2/3R-BP will be assessed by SPECT using the radioligand
[123I]-iodobenzamide (IBZM). IBZM has a European (CPMP) registration, and has
been shown to have no serious side effects. The dose equivalent per IBZM-SPECT
is 4.9 mSV (144MBq). Therefore, the total dose equivalent for each participant
will amount to less than 11.3mSv and 15.3mSv, which is the maximum
NCS-recommended dose for female research subjects >50 years and male subjects >
50 years respectively (risk category IIb). For the intragastric nutrient
infusions, a nasogastric tube will be inserted prior to brain imaging sessions.
To minimalize the risks associated with participation (tube complications,
radiation exposure), subjects with risk factors for tracheal tube placement
(e.g. swallowing disorder) and bleeding risk (use of anticoagulants) will be
excluded, tube tolerability will be assessed during a training session, and the
study is designed so that each participant will not be exposed to more than 2
SPECTs. Therefore, we believe that the scientific value of our findings will
outweigh the burden and risks associated with participation.
Meibergdreef 9
Amsterdam 1105AZ
NL
Meibergdreef 9
Amsterdam 1105AZ
NL
Listed location countries
Age
Inclusion criteria
Age: 50-70 years for female subjects and 40-70 years for male subjects, for
female subjects: postmenopausal, BMI <25 kg/m2 for lean subjects and >30 kg/m2
for obese subjects, insulin resistance for obese subjects, stable weight for 3
months prior to study inclusion
Exclusion criteria
Use of any medication except for those related to treatment of components of
the metabolic syndrome (not including insulin, oral glucose lowering drugs,
alpha- and beta-blockers)
Any actual medical condition except for treated hypothyroidism and the
metabolic syndrome
History of any psychiatric disorder, neurological disorders, eating disorders
(anorexia, binge eating, bulimia), alcohol abuse or upper gastrointestinal
tract surgery/abnormalities.
Shift work
Intensive sports (>3/week)
Restrained eaters
Smoking
XTC, cannabis, amphetamine or cocaine abuse
Alcohol abuse (>3 units/day)
Occupational radiation exposure
Contraindication for MRI
Lactose/gluten intolerance
Soya oil, egg or peanut allergy
Childhood onset of obesity (<4 years)
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| CCMO | NL61132.018.17 |
| OMON | NL-OMON28668 |