Clinical trial NCT02939703: Integrating Quantitative Energetics Determines the Microbiome's Contribution to Energy Balance
Official title: Integrating Quantitative Energetics Determines the Microbiome's Contribution to Energy Balance
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Obesity
Keywords: Adipose tissue
calorimetry
energy expenditure
microbiome
Lead sponsor: AdventHealth Translational Research Institute
Sponsor class: OTHER
Collaborators: name: Arizona State University
First posted: 2016-10-20
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: We propose to study the role of the gut microbiome in the development of obesity, and whether we can change the microbiome's contribution to host energy balance through diet. We have created a novel model that explicitly links the effects of microorganisms on human energy balance and modeled weight change, and will use the power of metabolic ward studies to measure small changes in energy absorption, total daily energy expenditure, and/or food intake that affect long-term weight gain or loss. By integrating clinical measurements, bioreactor experiments, and mathematical modeling, we will be able to describe cause-and-effect mechanisms that will enable a quantification of the microbiota's contribution to weight gain and inspire future studies on the interactions of diet, the gut microbiome, and human physiology.


Eligibility criteria: Inclusion Criteria:

1. Able to communicate meaningfully with the investigator and legally competent to provide informed written consent
2. Age 18 - 45 years, inclusive
3. Weight stable (+/- 3 kg) during the 6 months prior to enrollment
4. BMI ≤ 30 kg/m2

Exclusion Criteria:

1. History or presence of cardiovascular disease (unstable angina, myocardial infarction or coronary revascularization within 6 months, clinically significant abnormalities on EKG, presence of cardiac pacemaker, implanted cardiac defibrillator)
2. History of type 1 or type 2 diabetes
3. Bleeding disorders
4. Acute or chronic infections
5. Hepatitis and/or cirrhosis
6. Severe asthma or chronic obstructive pulmonary disease
7. Renal insufficiency or nephritis
8. Thyroid dysfunction (suppressed TSH, elevated TSH if symptomatic, elevated thyroid stimulating hormone (TSH) if asymptomatic)
9. Uncontrolled hypertension (BP \>160 mmHg systolic or \>100 mmHg diastolic)
10. Prior bariatric surgery
11. Inflammatory bowel disease or malabsorption, swallowing disorders, suspected or known strictures, fistulas or physiological/mechanical GI obstruction, history of gastrointestinal surgery, Crohn's disease or diverticulitis
12. Participants with strict dietary concerns (e.g. vegetarian or kosher diet, multiple food allergies, or allergies to food we will provide them during the study)
13. Current use of polyethylene glycol (e.g. Dulcolax, Miralax, Gavilax)
14. Cancer within the last 3 years (except non-melanoma skin cancer or treated cervical carcinoma in situ)
15. History of depression within \< 5 years from screening visit or which, in the opinion of a medical investigator, will impact the participant's ability to complete the study
16. History of eating disorders
17. Cushing's disease or syndrome
18. Untreated or inadequately controlled hypo- or hyperthyroidism
19. Active rheumatoid arthritis or other inflammatory rheumatic disorder
20. Pregnant or nursing females or females less than 6 months postpartum from the scheduled date of collection.
21. Tobacco use within the past 3 months
22. Metal implants (pace-maker, aneurysm clips) based on Investigator's judgment at Screening.
23. Unable to participate in MRI or MRS assessments due to physical limitations of equipment tolerances (e.g. MRI bore size) based on Investigator's judgment at Screening.
24. Unable to tolerate MRI/MRS imaging or claustrophobia.
25. Nickel allergy.
26. Had major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the pretrial (screening) visit.
27. Intolerance to acetaminophen use.
28. History of regular alcohol consumption exceeding 7 drinks/week for female participants or 14 drinks/week for male participants (1 drink = 5 ounces \[150 mL\] of wine or12 ounces \[360 mL\] of beer or 1.5 ounces \[45 mL\] of hard liquor) within 6 months before screening.
29. Anemia (hemoglobin \<12 g/dl in men, \<11 g/dl in women)

Primary outcomes:
measure: The primary endpoint for the protocol is the within-participant difference in fecal energy (via chemical oxygen demand, COD) normalized to the total daily energy intake and to the non-metabolizable marker PEG [COD (kcal) / PEG (g)].
timeFrame: Days 24-29 vs. Days 53-58
Secondary outcomes:
Other outcomes:
Locations:
city: Orlando
country: United States
facility: Translational Research Institute for Metabolism and Diabetes
state: Florida
Study officials:
affiliation: Study Principal Investigator
name: Steven R Smith, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Study Principal Investigator at Arizona State University
name: Rosa Krajmalnik-Brown, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Corbin KD, Krajmalnik-Brown R, Carnero EA, Bock C, Emerson R, Rittmann BE, Marcus AK, Davis T, Dirks B, Ilhan ZE, Champagne C, Smith SR. Integrative and quantitative bioenergetics: Design of a study to assess the impact of the gut microbiome on host energy balance. Contemp Clin Trials Commun. 2020 Aug 19;19:100646. doi: 10.1016/j.conctc.2020.100646. eCollection 2020 Sep.