The Lactate Project: Investigating the Impact of Lactate to Preserve Vital Organ Blood Supply and Function in Heart and Brain

The aim of the proposed study is to investigate the effect of increased plasma lactate concentrations on the heart and brain's metabolism of other energy sources, primarily glucose in the brain and glucose and FFA in the heart.

The investigator hypothesize that:

• An acute increase in lactate plasma concentration will decrease cerebral glucose uptake and increase cerebral blood flow
• An acute increase in lactate plasma concentration will decrease palmitate and glucose uptake in the myocardium, and increase myocardial perfusion

Study Overview

• Status: Not yet recruiting
• Conditions: Healthy; Lactate Blood Increase
• Intervention / Treatment: Other: Sodium Lactate Solution; Other: Saline infusion (placebo)

Detailed Description

SCREENING VISIT

During the initial screening visit, the investigators will inform all potential volunteers about the project, and volunteers will have the chance to ask questions about participation in the project.

The investigators will register the following data

1. Medical history to assess exclusion criteria
2. Weight, height, BMI
3. Standard medical examination including pulse, blood pressure and an ECG

After assessment of inclusion- and exclusion criteria remaining volunteers will be offered to participate in the project. The investigators will screen potential volunteers with the following blood samples: haemoglobin, HbA1c, glucose, cholesterol, triglyceride, TSH, creatinine, albumin, sodium, potassium, ALAT, ASAT, bilirubin and coagulation parameters.

Blood samples and randomization will not take place until volunteers have signed the informed consent form.

MAGNETIC RESONANCE IMAGING (MRI) SCAN

The investigators will perform a cerebral MRI for the purpose of anatomical localisation for alignment with the PET scans on the 1st and 2nd study day.

1st STUDY DAY:

The volunteers will arrive fasted (8 hours) at the Department of Nuclear Medicine & PET-Centre at 7.30 a.m., where the subject will have an arterial catheter placed for arterial blood sampling during PET scans as well as two venous catheters for blood sampling and continued administration of intravenous fluids (saline or Na-lactate) and adenosine. At 9.00 a.m., we will start the Na-lactate or saline infusion.

From 9.30 a.m., the investigators will perform PET scans with administration of relevant PET tracers preceding each scan. The investigators will perform PET scans in the following order:

1. Dynamic PET scan with [15O]H2O in order to assess cerebral perfusion.
2. Dynamic PET scan with [15O]H2O in order to assess myocardial perfusion.
3. Stress test using an adenosine infusion during a dynamic PET scan with [15O]H2O to assess coronary flow reserve (CFR) in the heart.
4. Dynamic PET scan with [11C]Palmitate to assess uptake, oxidation and re-esterification of FFA in the heart.
5. Dynamic PET scan with [11C]Acetate to asses oxygen and energy expenditure in the heart.
6. Dynamic whole-body PET scan with [18F]FDG to assess glucose uptake in the heart and brain.

Following the [11C]Acetate scan the investigators will administrate a continued infusion of insulin (0,3 mIE/kg/min) and 20% glucose throughout the rest of the study day in order to achieve hyperinsulinemic-euglycemic conditions (clamp conditions). To correct for attenuation, we will perform three lowdose, non-contrast enhanced CT scans over the course of the study day. The investigators will draw blood samples every hour.

2nd STUDY DAY

The PET scan regime during the 2nd study day is identical to the 1st study day. If volunteers were administered Na-lactate during the 1st study day they will be administered saline during the 2nd studyday and vice versa.

• Study Type: Interventional
• Enrollment (Estimated): 8
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Esben Søndergaard, MD, PhD; Phone Number: 004528730943; Email: Esben.sondergaard@clin.au.dk
• Study Contact Backup: Name: Jens Voigt, MD; Phone Number: 0026395294; Email: Jens.voigt@clin.au.dk

Study Locations

• Denmark
  • N
    • Aarhus, N, Denmark, 8000
      • Medical Research Laboratories/Steno Diabetes Center Aarhus
      • Contact: Esben Søndergaard, MD, PhD; Phone Number: 00‭28 73 09 43‬; Email: Esben.sondergaard@clin.au.dk
      • Contact: Jens Hohwü Voigt, MD; Phone Number: 0026395294; Email: Jens.voigt@clin.au.dk
    • Aarhus, N, Denmark, 8200
      • Department of Nuclear Medicine & PET-Centre
      • Contact: Jens Hohwü Voigt, MD; Phone Number: 0026395294; Email: Jens.voigt@clin.au.dk
      • Contact: Lars Christian Gormsen, MD, PhD, Proffessor; Phone Number: 00‭22 81 16 31‬; Email: lars.christian.gormsen@clin.au.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Age 55-75 years
2. Male or postmenopausal female
3. BMI 20-35 kg/m2
4. Signed informed consent form

Exclusion Criteria:

1. Clinically significant heart, lung, kidney, kidney, liver, endocrine or malignant disease basedon information obtained during an initial screening visit as well as blood samples and an ECG.
2. Blood donation within the last 3 months
3. Smoking
4. Alcohol- or substance abuse
5. Participation in other clinical trials involving ionized radiation within the last 6 months
6. Claustrophobia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Na-Lactate infusion	Other: Sodium Lactate Solution; Infusion of sodium-lactate solution
Placebo Comparator: Saline infusion (Placebo)	Other: Saline infusion (placebo); NaCl solution; Other Names: NaCl

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cerebral glucose uptake	Cerebral glucose uptake ([18F]FDG PET scan) under basal and hyperinsulinemic- euglycemic conditions (clamp conditions).	From T=300-360 (minutes)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cerebral blood flow	Cerebral blood flow ([15O]H2O PET scan)	T = 0-10 (minutes)
Myocardial perfusion	Myocardial perfusion ([15O]H2O PET scan)	T = 0-10 (minutes)
Myocardial glucose uptake	Myocardial glucose uptake ([18F]FDG PET scan)	T = 300-360 (minutes)
Myocardial FFA uptake and oxidation	Myocardial FFA uptake and oxidation ([11C]Palmitate PET scan)	T = 30-70 (minutes)
Myocardial contractility	Myocardial contractility (ejection fraction based on ECG-gated PET scan)	T=0-10 (minutes)
Myocardial oxygen consumption and efficiency	Myocardial oxygen consumption and efficiency ([11C]Acetate PET scan)	T=150-180 (minutes)
Blood sampling	A number of cardiometabolic blood samples will be collected during the whole study day.	T = -60 to 360 (minutes)

Collaborators and Investigators

• Sponsor: University of Aarhus
• Collaborators: Aarhus University Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2025
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: October 29, 2024
• First Submitted That Met QC Criteria: October 29, 2024
• First Posted (Actual): October 30, 2024

Study Record Updates

• Last Update Posted (Estimated): November 1, 2024
• Last Update Submitted That Met QC Criteria: October 30, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Lipid metabolism; Glucose metabolism; Cerebral metabolism; Human metabolism; Cardiac metabolism; Substrate utilization; Cerebral blod flow; Cardiac perfusion; Lactate utilization
• Additional Relevant MeSH Terms: Metabolic Diseases; Hyperlactatemia
• Other Study ID Numbers: THE LACTATE PROJECT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No