Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT05232812 |
| Other study ID # |
1-10-72-290-20 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
June 1, 2022 |
| Est. completion date |
March 29, 2023 |
Study information
| Verified date |
January 2023 |
| Source |
University of Aarhus |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Ketone bodies are produced in the liver at high levels of fatty acids, and act as an
important source of energy for the brain and heart during fasting. The energy production from
ketone metabolism is less oxygen-demanding than both glucose and fatty acid metabolism, and
ketone substances can therefore be a very energy-efficient substrate for the heart.
Insulin-resistant people as well as people with heart disease have difficulty burning glucose
in the heart due to the insulin resistant condition and are therefore dependent on other
energy sources such as free fatty acids and ketones. Because ketones are oxygen-sparing
compared to fatty acids, interventions that increase the level of ketone bodies can
potentially reduce the heart's need for oxygen in patients with narrowed coronary arteries.
PET/CT is a functional and non-invasive imaging modality and suitable for tracking the fate
of metabolites non-invasively, as most substrates or metabolites can be labeled by a PET
isotope.
The purpose of this experiment is therefore to validate a new ketone tracer called
3-[11C]-OHB. Implementation of the 3-[11C]-OHB tracer will in future allow the investigators
to more directly estimate the impact of different levels of ketone bodies on organ functions
by measuring tissue-specific ketone uptake, both after intravenous and oral administration.
Description:
Background:
Ketone bodies consists of 3-hydroxybutyrat, acetoacetate, and acetone. They are produced in
the liver at high levels of fatty acids, and act as an important source of energy for the
heart, brain and skeletal muscle during fasting. Energy production by ketone metabolism is
less oxygen-intensive than both glucose and fatty acid metabolism, and ketone substances can
therefore be a highly energy-efficient substrate. Insulin resistant individuals as well as
people with heart disease have difficulty utilising glucose in the heart due to the insulin
resistant condition and are therefore dependent on other energy sources such as free fatty
acids and ketones. Because ketones are oxygen sparing compared to fatty acids, interventions
that increase the level of ketone bodies can potentially reduce the heart's need for oxygen
in patients with narrowed coronary arteries. This has led to an increased focus on the
potential of ketone bodies in the treatment of a number of diseases, including especially
cardiovascular disease.
Our group has shown that ketone bodies are efficiently absorbed by the heart despite maximal
stimulation with insulin and glucose. In the study, healthy subjects increased the level of
circulating ketone bodies to approximately 4 millimolar with a continuous ketone infusion,
which resulted in a 50% reduction in cardiac glucose consumption. Since the consumption of
free fatty acids in the experiment was unchanged and the overall work of the heart was the
same, up to 50% of the heart's energy consumption was thus covered by ketone bodies. In
addition, the high levels of ketone bodies led to a marked increase in the blood flow to the
heart, which could potentially further benefit patients with narrowed coronary arteries
PET/CT is a functional and non-invasive imaging modality that is well established in
oncological staging and treatment monitoring. The technique is also suitable for tracking the
fate of metabolites non-invasively, as most substrates or metabolites can be labeled by a
suitable PET isotope. PET has sufficient spatial and temporal resolution to enable direct
quantification of e.g. uptake and oxidation rates and has been successfully used by our
department to assess heart efficiency, oxygen consumption and fatty acid metabolism.
Purpose With this study, the investigators want to determine the metabolism of ketone bodies
in healthy individuals and validate a newly developed ketone PET tracer for use in humans
called 3-[11C]-OHB. Previous studies conducted by our and others' groups have only been able
to indirectly estimate the uptake of ketone bodies into the heart. With 3-[11C]-OHB, the
investigators will be able to directly measure tissue-specific ketone uptake, both after
intravenous and oral administration.
Ihe investigators will apply state-of-the-science PET/CT tracer techniques and
well-established models for estimating ketone metabolism (kinetics) and the radiation
exposure of the tracer. Implementation of the 11C-3-OHB tracer in the future will allow the
investigators to more directly estimate the impact of different levels of ketone bodies on
organ functions, not least in the heart.
In this study, the investigators plan specifically
- To investigate the biodistribution and kinetics of the tracer 3-[11C]-OHB
- To estimate the radiation exposure of 3-[11C]-OHB by intravenous and oral administration
of the tracer
Methods:
Six healthy and overweight (BMI: 28-40 kg/m^2) aged 50-70 years will undergo two PET/CT scans
with 3-[11C]-OHB. One scan will be performed with the injection of 200 MBq of tracer and the
other one will be performed with the subjects orally ingestion 100 MBq of the tracer.
Following administration of the tracer, dynamic PET scans over the whole body will be
performed to measure the biodistribution and radiation exposure of the tracer.
