Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04308577 |
| Other study ID # |
U Copenhagen |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
October 5, 2020 |
| Est. completion date |
May 31, 2021 |
Study information
| Verified date |
July 2021 |
| Source |
University of Copenhagen |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Each year, approx. 100 patients with severe brain injury is admitted to the Clinic for
Neurorehabilitation/TBI Unit, Rigshospitalet. Severe brain injury results in local oxygen
deficiency and acid formation in the brain, which together destroys brain cells. The purpose
of this study is to investigate whether it is possible to carry out a ketogenic diet therapy
for patients with severe brain injury for six weeks. Ketosis has been shown to be
neuroprotective during and after severe brain injury.
Description:
Abstract
At the Department of Highly Specialized Neurorehabilitation/Traumatic Brain Injury,
Rigshospitalet (satellite department at Hvidovre Hospital), approximately 100 patients (pt.)
are admitted with severe brain damage every year. From 2015 to 2017, 305 pt. were admitted.
Out of the 305 pt., 162pt. (53%) had traumatic brain injury (TBI), 48pt. (16%) had apoplexy,
35pt. (12%) had other diagnoses (infections, tumors and almost drowning, etc.), 20pt. (7%)
had spontaneous subarachnoid hemorrhage (SAH) and 24pt. (8%) had brain damage as a result of
cardiac arrest.
TBI is a leading cause of injury-related morbidity and mortality worldwide. According to the
Global Burden of Disease Study (2016), there were 27,08 million new cases of TBI globally in
2016. In Denmark, there were 17.302 new cases of TBI in 2016. Clinical studies have
repeatedly shown major changes in cerebral energy metabolism after TBI. The secondary brain
injury leads to metabolic cellular dysfunction, cerebral edema, and a complex injury cascade.
The injury spread includes processes such as inflammation, edema, free radical damage,
oxidative damage, ischemic injury, cerebral glucose metabolism disorder, and ion-mediated
cell damage. Much of the neurological dysfunction that occurs in acute TBI also occurs in
apoplexy, SAH and cerebral ischemia.
A very important adaptive metabolic response after brain injury is the utilization of
alternative cerebral energy substrates, including lactate, but also ketone bodies (KB) such
as β-hydroxybutyrate (BHB) and acetoacetate (AcAc). In addition to having a central role in
the regulation of cerebral energy metabolism after brain injury, KB has other important
neuroprotective properties, including attenuation of oxidative stress, apoptotic cell death,
and microglial activation. Increasing KB metabolism through fasting or diet-induced ketosis
promotes brain resistance to stress and injury, and attenuates acute cerebral injury.
Therefore, supplementing with KB, e.g. through the use of a ketogenic diet (KD) with added
medium chain fatty acids (MCT), has emerged as a potential non-pharmacological
neuroprotective therapy.
KD has been used for many years for the treatment of refractory epilepsy in children and
studies done on adults show promising results, but experience from several studies shows
major compliance issues. KD has been shown to reduce cerebral edema and apoptosis, as well as
improve cerebral metabolism and behavioral outcomes in TBI rodent models, but clinical human
trials on adults with TBI are lacking. Apoplexy animal models show positive effects on
pathological and functional outcomes of KD intervention or exogenous ketone administration.
The only human trial of KD and apoplexy shows that KD is safe and tolerated by patients with
acute apoplexy. Our hypothesis is that diet-induced ketosis will reduce the extent of
secondary brain damage. The purpose of the trial is to investigate whether an intervention
with a ketogenic diet supplemented with MCT is feasible for 6 weeks on hospitalized pt. with
severe brain damage. This is the pre-study for a controlled study.
