Lactate in the Gut

NCT04299815 | Completed

• 1 other identifier: 1-10-72-8-20
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Lactate is formed naturally in the body in example during physical activity. However, lactate is also formed during food fermentation where certain bacterial strains form lactate. Lactate can also be produced chemically. An example of this is Ringer-lactate which is used for volume replacement when treating dehydrated patients. As a source of carbon-molecules, lactate is believed to be an important oxidative fuel source in all major organs and yields adenosine triphosphate (ATP) production through Krebs cycle, the Electron Transport Chain in the mitochondria as well as by being a key precursor for gluconeogenesis. Metformin is the first drug of choice for type 2 diabetes treatment. Use of metformin often results in a small but significant weight loss in overweight users. It is known that metformin increases the lactate concentration in the gut. It is also known also know that metformin use is associated with an increase in blood concentrations of growth differentiation factor 15 (GDF-15). Receptors for GDF-15 can be found in parts of the brain associated with control of appetite. In rats increases in \[GDF-15\] results in a decrease in appetite and thus weight loss. GDF-15 is thought to be involved in the normal energy homeostasis. With this study the investigators want to examine the hormonal, metabolic and mechanical effects of lactate in the gut in healthy volunteers. Our hypothesis is that lactate has beneficial effects which may be though an increase in GDF-15 in the blood. Volunteers will undergo two study days separated by at least 7 days and a maximum of 1 month.

• On day one volunteers will drink a sodium-lactate solution (intervention). The investigators will also administrate 1500mg paracetamol to assess gastric emptying and do blood samples over 4 hours. The investigators measure \[lactate\] every 15 min. Every hour the investigators will ask volunteers questions regarding hunger and thoughts of future food intake (questionnaire). After 4 hours of blood sampling the investigators will serve volunteers an all-you-can-eat meal of sandwich and measure how must they ate.
• On day two volunteers will drink a sodium chloride solution. Furthermore, the investigators administrate intravenous D/L sodium lactate in order to reach the same plasma \[lactate\] on day 2 as was done on day 1. The rest of day two is identical to day 1.

Conditions

Lactate; Healthy; Hyperlactatemia

Keywords

lactate; metabolism; Gastric emptying; GDF-15; insulin; incretin hormones

Outcome Measures

Primary Outcomes (1)

• GDF-15

  Difference in \[GDF-15\] between intervention and placebo

  4 hours

Secondary Outcomes (10)

• glucagon-like peptide -1

  4 hours

• Gastric inhibitory peptide (GIP)

  4 hours

• free fatty acid

  4 hours

• cholecystokinin

  4 hours

• Ghrelin

  4 hours

Study Arms (2)

Oral lactate

ACTIVE COMPARATOR

Sodium D/L lactate solution, 25g/L in 300mL water

Drug: Oral Sodium Lactate

Iso-lactic intravenous lactate infusion

PLACEBO COMPARATOR

iv sodium D/L lactate to elevate \[lactate\] to the same levels as measured on day 1 + oral sodium chloride, 300 mL

Drug: Intravenous sodium lactate

Interventions

Oral Sodium Lactate DRUG

25 grams of D/L lactate dissolved in 300mL water.

Oral lactate

Intravenous sodium lactate DRUG

intravenous sodium lactate + oral sodium-chlorid solution

Iso-lactic intravenous lactate infusion

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male gender
• Age 18-50 years
• BMI 20-30 kg/m2
• In good health with no daily use of prescription medicine based on medical history, clinical examination and blood samples.
• Spoken and written informed consent

You may not qualify if:

• Chronic illness or daily use of prescription medicine .
• Abnormal screening blood samples as judged by the PI
• Does not understand or speak Danish

Sponsors & Collaborators

• University of Aarhus: lead

Study Sites (1)

Aarhus University Hospital

Aarhus, 8200, Denmark

Location

Related Publications (2)

• Pedersen MGB, Lauritzen ES, Svart MV, Stoy J, Sondergaard E, Thomsen HH, Kampmann U, Bjerre M, Jessen N, Moller N, Rittig N. Nutrient sensing: LEAP2 concentration in response to fasting, glucose, lactate, and beta-hydroxybutyrate in healthy young males. Am J Clin Nutr. 2023 Dec;118(6):1091-1098. doi: 10.1016/j.ajcnut.2023.10.007. Epub 2023 Oct 14.

  PMID: 37844838 DERIVED

• Pedersen MGB, Sondergaard E, Nielsen CB, Johannsen M, Gormsen LC, Moller N, Jessen N, Rittig N. Oral lactate slows gastric emptying and suppresses appetite in young males. Clin Nutr. 2022 Feb;41(2):517-525. doi: 10.1016/j.clnu.2021.12.032. Epub 2021 Dec 24.

  PMID: 35016146 DERIVED

MeSH Terms

Conditions

Hyperlactatemia; Insulin Resistance

Interventions

Sodium Lactate

Condition Hierarchy (Ancestors)

Metabolic Diseases; Nutritional and Metabolic Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Hyperinsulinism; Glucose Metabolism Disorders

Intervention Hierarchy (Ancestors)

Lactates; Hydroxy Acids; Carboxylic Acids; Organic Chemicals

Study Officials

• Nikolaj Rittig, postdoc

  Steno Diabetes Center Aarhus (SDCA), Aarhus universitetshospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 5, 2020
• First Posted: March 9, 2020
• Study Start: April 1, 2020
• Primary Completion: July 29, 2020
• Study Completion: July 29, 2020
• Last Updated: September 30, 2020

Record last verified: 2020-02

Locations

DK (1)