13C Trioctanoate Breath Test as a Measurement of Gastric Fat Volume Emptying
Condition: Healthy
Study type: Interventional
Phase: Early Phase 1

Summary: 
      13C breath tests represent an attractive alternative in the measurement of gastric emptying
      (GE). Therefore these tests have been used in a variety of clinical settings such as in the
      assessment of gastroparesis, delayed GE in diabetic patients or in the assessment of GE with
      fat containing enteral formulas in critically ill patients.

      The investigators have previously demonstrated that the 13C sodium octanoate breath test
      (OBT) is an inappropriate measurement method for the GE of fat. The OBT appears to be
      affected by 1) post gastric processing of the OCC marker and 2) its interaction with the
      physical form and concentration of the fat present in the stomach and duodenum.

      The13C trioctanoate breath test (TriOBT) represents an attractive alternative to the OBT.
      Compared to OCC which is a medium chain fatty acid the 13C trioctanoate (TriOCC) is a
      triglyceride. TriOCC has similar physio chemical properties as the nutritional lipid e.g.
      rapeseed oil.

      This study aims to assess the efficacy of the TriOBT as a GE measurement method of fat in an
      acid stable lipid emulsion (LE1). The breath test results from the TriOBT will be compared
      with the OBT and further validated against gastric fat volume emptying data observed from
      MRI. The interim analysis will determine whether the study will proceed to stage 2 which will
      assess the efficacy of the TriOBT in an acid unstable lipid emulsion (LE4).
    

Detailed description: 
      13C breath tests for the measurement of gastric emptying (GE) were first developed in the
      early 1990s. These tests have clear advantages over many other GE imaging techniques as they
      are relatively inexpensive, simple to use, can be carried out in children and pregnant women
      or those who have contraindications to MRI. Therefore these tests have been used in a variety
      of clinical settings such as in the assessment of gastroparesis or delayed GE in diabetic
      patients or the assessment of GE with fat containing enteral formulas in critically ill
      patients. Breath tests rely upon the ingestion of a 13C stable isotope markers such as the
      medium chain fatty acid 13C octanoic acid (OCC) and the tryglyceride13C trioctanoate
      (TriOCC).

      However, 13C breath tests are an indirect measure of GE. Thus, GE data acquired from breath
      tests are a result of numerous complex interactions which include: 1) the chemical properties
      of markers and their interactions with test meals during gastric processing 2) absorption
      from the duodenum, 3) metabolism by the liver (oxidation of fatty acids) and 4) final
      excretion as 13CO2 by the lungs. All of these complex interactions can become compounded when
      the gastric processing of lipid emulsions (LEs) are investigated and thus careful
      consideration and selection of breath test markers is required.

      The investigators have developed isocaloric and isovolume LEs with different GE properties as
      shown previously with MRI. The acid stable (LE1) and acid unstable lipid emulsion (LE4)
      responds differently to the conditions within the stomach. LE1 empties relatively uniformly
      from the stomach. However, the LE4 separates into water and high fat phases after 15-30 min
      of being in the stomach. In the late phase of GE the emulsion is re-emulsified and thus there
      are three distinct GE phases in LE4. Once separation of LE4 occurs the aqueous and low fat
      phase empties fairly rapidly from the stomach whereas the second fat phase empties more
      slowly. The differing GE pattern of acid unstable LEs has a profound effect on GE breath test
      data dependent upon the selection of the breath test marker used.The investigators have
      previously demonstrated that the OCC breath test (OBT) is an inappropriate measure of the
      gastric emptying of fat as the OBT is influenced by 1) Post gastric processing of the OCC
      marker and 2) its interaction with the physical form and concentration of the fat present in
      the stomach and duodenum. These effects were highlighted by only a marginal concordance
      agreement with the OBT half emptying (T50) of 13CO2 recovery and fat volume T50 (MRI T50)
      with LE1 and no agreement with LE4 (rc=0.7 and rc=0.4 respectively)..

      The main aim of this study is to investigate whether TriOCC is a more appropriate breath test
      marker to use in the measurement of the GE of fat. As the TriOCC is a triglyceride it has
      similar physiochemical properties to nutritional lipids. Therefore, it is more likely to
      behave similarly in the gastric and duodenal environment to ingested lipids in emulsions such
      as rapeseed oil. In study 1 the investigators will compare the breath test markers TriOCC and
      OCC in LE1. In a sub set of participants a validated MRI quantitative fat fraction method
      will be used to determine reference values for the half gastric emptying time of fat (MRI
      T50). This will be correlated to half emptying (T50) of 13CO2 recovery generated from
      percentage dose recovery per hour (PDR/h) curves. The interim analysis will assess whether
      the TriOCC is more related to gastric fat volume emptying than the OCC marker in LE1. Should
      TriOCC be representative of gastric fat volume emptying study 2 will then proceed. Study 2
      will then assess the gastric emptying of fat as above but with LE4.

      A secondary aim is to develop an algorithm to quantify the heterogeneity of fat distribution
      within gastric content for MRI data. The gastric processing of lipid emulsions as visualized
      by MRI has been shown to result in a large inter individual variation of fat distribution. By
      quantifying this heterogeneity we aim to determine the degree of flocculation and creaming of
      the emulsions across the length of the stomach.
    

Intervention name(s): Octanoic acid (1-13C, 99%); TRIOCTANOIN (1,1,1-13C3, 99%)
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): 13C-marker will be mixed with emulsions. 2 isovolumetric (200 ml) and isocaloric (200 kcal) lipid emulsions with different acid and shear stability Lipid emulsion 1: acid stable, particle size 0.6 µm
Optional study pending interim analysis:
Lipid emulsion 4: acid unstable, redispersible by mechanical processes during antral contractions and passage through the pylorus, particle size 0.6 µm; 13C-marker will be mixed with emulsions 2 isovolumetric (200 ml) and isocaloric (200 kcal) lipid emulsions with different acid and shear stability
Lipid emulsion 1: acid stable, particle size 0.6 µm
Optional study pending interim analysis:
Lipid emulsion 4: acid unstable, redispersible by mechanical processes during antral contractions and passage through the pylorus, particle size 0.6 µm
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Participant)
Primary purpose: Basic Science
Keywords: breath test; lipid emulsions; MRI; gastric emptying