Brown Adipose Tissue in ALS
Condition: Amyotrophic Lateral Sclerosis
MeSH terms: Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Sclerosis
Study type: Interventional

Summary: 
      Weight loss is a common phenomenon in ALS. During the course of the disease, difficulty in
      swallowing and mastication can be responsible for a decrease in caloric intake and thus for
      weight loss. However, significant weight loss can also be observed in patients with no
      feeding difficulties. About half of ALS patients have an increase in their resting energy
      consumption, but the origin of this "hypermetabolism" remains unknown. "Brown" fat is
      specialized in the production of heat. Unlike "white" fat that stores excess caloric intakes,
      brown fat consumes energy. In humans, brown fat has long been considered as absent in adults.
      However, recent imaging techniques have been able to detect brown fat deposits in some adult
      subjects. The aim of this study is thus to determine the role of brown fat on energy
      consumption in Amyotrophic Lateral Sclerosis.
    

Detailed description: 
      Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder involving
      motor neurons of the cerebral cortex, brain stem and spinal cord. Motor neuron loss results
      in rapidly progressive muscle paralysis, usually leading to death from respiratory failure in
      3-5 years.

      Weight loss is a frequent phenomenon and an independent negative prognostic factor for
      survival in ALS. Involvement of bulbar muscles with dysphagia is likely to lead to decrease
      in energy intake resulting in negative energy balance. However, weight loss also occurs in
      non-dysphagic patients, and is not restricted to reduction in skeletal muscle mass but also
      involves fat mass reduction.

      Hypermetabolism (i.e. elevation of resting energy expenditure, REE) have been reported in ALS
      in about 50% of ALS patients but the origin of this hypermetabolism remains unknown. Increase
      of REE seems paradoxical in the context of ALS because skeletal muscle mass, which accounts
      for a large proportion of energy consumption and heat production, is decreased in ALS
      patients. Brown adipose tissue (BAT) is another important organ for basal and inducible
      energy expenditure and thermogenesis. In humans, BAT is primarily found in infants and young
      children, and healthy adults has long been considered as almost devoid of functional BAT.
      However, a recent study using 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomographic
      (PET) scan showed that depots of functional BAT were present in about 5% of adult humans,
      most commonly localized in the cervical-supraclavicular region. In an autopsy series, depots
      of BAT in the periadrenal region were found in 19/20 ALS patients. It has been estimated
      that, if present, 50 g of maximally stimulated brown tissue could represent up to 20% of REE
      expenditure in an adult human. The presence of substantial, functional, depots of BAT could
      thus participate in the increase of REE observed in ALS patients.

      The primary objective of this study is to identify and quantify potential depots of
      functional BAT in ALS patients. Secondary objectives will be to correlate amount of
      detectable BAT with measured REE, clinical parameters evaluating ALS progression and
      biological parameters.

      This study will include 5 patients referred to the Paris ALS center with a diagnosis of ALS
      and "unexplained" (i.e. not explained by severe dysphagia) loss of 5 percent or more of
      normal body weight in the last 6 months. 5 ALS patients without significant weight loss will
      also be included in the study as controls.

      For each patient, measurement of REE will be performed by indirect calorimetry. The volume
      and activity of BAT will be determined using 18F-FDG PET whole body scans. Data on
      concomitant and past disorders (including cancer and diabete mellitus), smoking history,
      medication use, height, current and normal body weight, age and site of onset of ALS symptoms
      will be recorded. Functional motor impairment will be assessed using manual muscle testing
      and the revised ALS Functional Rating Scale as in routine clinical practice.

      This study will be the first to investigate, using non-invasive procedures, the role of
      depots of functional BAT in ALS patients' metabolic dysfunction. The results will provide new
      insights on the origin and consequences of the dysregulation of metabolic homeostasis in ALS.
    

Intervention name(s): Indirect Calorimetry.; 18-FDG-PET
Intervention type(s): Other; Device
Intervention description(s): REE measurement; 18-FDG-PET
Intervention MeSH terms: Fluorodeoxyglucose F18
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Other