Ketogenic Diet to Improve Neuro-recovery
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|ClinicalTrials.gov Identifier: NCT03509571|
Recruitment Status : Recruiting
First Posted : April 26, 2018
Last Update Posted : October 27, 2021
|Condition or disease||Intervention/treatment||Phase|
|Spinal Cord Injuries||Other: Ketogenic Diet Other: Standard Diet||Not Applicable|
There is an urgent need for innovative therapies for improving neurorecovery after spinal cord injury (SCI). Despite extensive research, clinical advancements, and improved rehabilitation strategies, SCI continues to be a significant cause of disability and mortality. After a primary impact, the injured spinal cord undergoes multiple secondary pathological states that represent an important target in developing neuroprotective strategies for treatment of SCI. Even minor improvements in neurological recovery can have profound impacts on management of daily activities, secondary health complications, and quality of life. Thus, timely and effective strategies are of critical importance for positive outcomes after SCI. A number of pharmacological neuroprotective agents have been subject to intensive investigation in large, multicenter, prospective randomized controlled trials. Despite promising preclinical animal data, the primary outcomes of these clinical trials were largely negative. There is thus clear reason for researchers, clinicians, and patients to seek alternative therapies to enhance neurorecovery and functional status after SCI.
The scientific premise of this project rests upon accumulating evidence that diet-based therapies, such as the ketogenic diet (KD), offer effective neuroprotection against secondary injury cascades and improve forelimb motor function in a rat model of SCI and improve upper extremity motor function in patients with acute SCI. The KD is a high-fat, low-carbohydrate diet designed to mimic the metabolic and biochemical changes that occur during calorie restriction, specifically ketosis. Ketone bodies have been shown to exert neuroprotective effects by preventing oxidative damage; attenuating neuroinflammation and glutamate excitotoxicity; and inhibiting apoptosis in the brain and spinal cord. Because glutamate excitotoxicity, inflammation, and induction of apoptotic pathways lead to progressive degeneration in the spinal cord shortly after the injury, inhibition of these processes by ketone bodies may enhance neurological recovery after an SCI. In support of these hypotheses, we recently showed for the first time that, compared with a standard hospital diet (SD), 5 weeks of KD improved upper extremity motor function in patients with acute SCI. In addition, a neuroinflammatory blood protein, fibrinogen, was present at lower levels in the KD serum samples than in the SD serum samples. Taken together, our results suggest that a KD may induce anti-inflammatory effects in part by reducing fibrinogen, which promotes neuroprotection and improved recovery.
The acute stage post-SCI is also characterized by hyperglycemia, which is strongly associated with poor functional outcomes at discharge. These findings support the importance of achieving tight glycemic control in acute human SCI to obtain better neurological outcomes. Emerging evidence suggests that a KD can also improve the patient's metabolic state and maintain normal glycemic levels. In contrast, standard hospital diets have traditionally promoted a relatively high carbohydrate nutritional content. Consistent with previous findings, we have recently shown that 5 weeks of KD decreased fasting serum glucose levels by 24 mg/dl whereas levels increased by 0.7 mg/dl in the SD group. These provocative findings have led us to our central hypothesis that SCI patients who consume a KD over the first 5 weeks (average hospital stay) after injury will have better neurological recovery, functional independence, and glycemic control than the SCI patients who consume an SD during this period.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||60 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Single (Outcomes Assessor)|
|Official Title:||Evaluation of a Ketogenic Diet for Improvement of Neurological Recovery in Individuals With Acute Spinal Cord Injury|
|Actual Study Start Date :||May 9, 2019|
|Estimated Primary Completion Date :||February 1, 2024|
|Estimated Study Completion Date :||February 28, 2024|
Experimental: Ketogenic Diet Group
Ketogenic diet is a high-fat, low-carbohydrate diet (lipid to carbohydrate + protein ratio of 3:1) that included ≈72% total energy as fat, ≈25% as protein, and ≈3% as carbohydrate during enteral feeding and ≈65% total energy as fat, ≈27% as protein, and ≈8% as carbohydrate and fiber during solid feeding. Patients will start receiving ketogenic diet within the 72 hours injury, after completing their baseline measurements.
Other: Ketogenic Diet
Enteral feeding via nasogastric (NG) or nasojejunal (NJ) tubes with ketogenic diet will start within 72 hours of injury and solid feeding will start as soon as the patient is able to swallow. This diet is a high-fat, low-carbohydrate diet (lipid to carbohydrate + protein ratio of 3:1) that will include ≈75% total energy as fat, ≈20% as protein, and ≈5% as carbohydrate and fiber.
Standard Diet Group
Patients will start to receive standard hospital diet within 72 hours of injury after completing their baseline measurements. Standard diet includes ≈35% total energy as fat, ≈27% as protein, and ≈44% as carbohydrate and fiber.
Other: Standard Diet
Enteral feeding via nasogastric (NG) or nasojejunal (NJ) tubes with SD diet will start within 72 hours of injury and solid feeding will start as soon as the patient is able to swallow. This diet includes ≈35% total energy as fat, ≈27% as protein, and ≈44% as carbohydrate and fiber.
- Change in sensory and motor function [ Time Frame: Baseline (within 72 hours of injury), 3 and 5 weeks ]The ASIA Motor Index Score will be used for measuring motor function. This index uses standard manual muscle testing on a six grade scale. The total possible score from upper and lower extremity is 50. For the sensory examination, each dermatome will be tested for both sharp (pin-prick) and light-touch sensation and will be graded on a three point scale. Numerically, the sensory scores total 116 points. Measurement of motor and sensory function will take about an hour and will be performed 3 times during the course of the study.
- Change in serum glucose concentration [ Time Frame: Baseline (within 72 hours of injury), 3 and 5 weeks ]Oral glucose tolerance test will be given to measure serum glucose concentration (mg/dl) after overnight fasting.
- Change in functional Independence [ Time Frame: Baseline (within 72 hours of injury), 3 and 5 weeks ]The Spinal Cord Independence Measure (SCIM) will be used for measuring functional independence. The SCIM is, at present, the only comprehensive rating scale that measures the ability of patients with SCI to perform everyday tasks according to their value for the patient. It requires no manual testing and the range of the total score is 0 to 100.
- Change in serum biomarkers for neurorecovery [ Time Frame: Baseline (within 72 hours of injury), 3 and 5 weeks ]Targeted proteomics analysis in serum samples will be used to quantify proteins and peptides known to be involved in neuro-inflammation in the acute stages of spinal cord injury including fibrinogen, extracellular signal-regulated kinase, ½, CD11b/CD18 integrin receptor, and epidermal growth factor receptor.
- Change in serum insulin concentration [ Time Frame: Baseline (within 72 hours of injury), 3 and 5 weeks ]Oral glucose tolerance test will be given to measure serum insulin concentration (μU/ml ) after overnight fasting.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03509571
|Contact: Ceren Yarar-Fisher, PhDemail@example.com|
|United States, Alabama|
|Birmingham, Alabama, United States, 35294|
|Contact: Ceren Yarar-Fisher, PhD|
|Principal Investigator:||Ceren Yarar-Fisher, PT, PhD||University of Alabama at Birmingham|