Randomized Controlled Trial of Time-Restricted Feeding (TRF) in Acute Ischemic Stroke Patients

Not Applicable

Interventions: Behavioral: Time-restricted feeding (TRF) with dietary counseling

Brief Summary: Many preclinical studies have demonstrated the beneficial effects of intermittent fasting (IF) in a wide range of neurological and cardiovascular diseases. This pilot study aims to investigate the safety and compliance as well as efficacy of one specific IF intervention called time-restricted feeding (TRF; 16 hours fasting daily) in patients with acute ischemic stroke (AIS).

Detailed Description: Specific Aims This project is to conduct a pilot, phase II randomized clinical trial which aims to investigate the safety and compliance as well as efficacy of one specific IF intervention called time-restricted feeding (TRF; 16 hours fasting daily) in patients with acute ischemic stroke (AIS) The primary endpoint is the safety and compliance of 4 weeks of TRF in AIS patients.

The secondary endpoints are the efficacy of 4 weeks of TRF compared to normal eating (NE) on plasma and imaging biomarkers and functional outcome at 3 months post-stroke.

This study will determine whether compared to NE control:

1. TRF (16 hours fasting daily) is safe and well-tolerated in patients with AIS.

2. TRF improves functional outcome compared to NE in AIS patients. (3) TRF decreases plasma pro-inflammatory cytokines including metallopeptidase (MMP)-9, interleukin (IL)-6, and tumor necrosis factor alpha (TNF) in plasma compared to baseline and NE in AIS patients.

(4) TRF improves diffusion tensor imaging on MRI at 3 months post stroke compared to baseline and NE in AIS patients.

(5) TRF changes plasma exosome components, metabolomics and lipidomics compared to baseline and NE in AIS patients.

Recruitment & Eligibility

Inclusion Criteria

Exclusion Criteria

Large hemispheric (> 1/2 middle cerebral artery territory) or cerebellar (>3 cm in diameter) infarct
Receiving intravenous rt-PA (alteplase) or endovascular thrombectomy
Severe stenosis (> 50%) or occlusion of intra/extra cranial arteries corresponding to acute ischemic stroke territory.
Body mass index ≤ 24.
Active cancer.
Diabetes mellitus (ex. HbA1C > 7% or taking oral hypoglycemic agent or insulin)
Active gastrointestinal bleeding.
Active infection, concurrent steroid usage or specific endocrine disorders.
Pre-stroke modified Rankin Scale > 2
Not willing to participate the trial.

Arm && Interventions

Group	Intervention	Description
Time-restricted feeding (TRF) with dietary counseling	Time-restricted feeding (TRF) with dietary counseling	1. Subjects will be instructed to eat ad libitum from 10:00 to 18:00 h daily, and fast from 18:00 to 10:00 h daily. During the 8-h feeding window, there will be no restrictions on types or quantities of foods consumed. During the fasting period, subjects will be encouraged to drink plenty of water and will be permitted to consume energy-free beverages. 2. Subjects will complete a 3-d food record (2 regular day and 1 holiday) each week during the experiment. 3. The blood draws will be taken at approximately 11:00 am, especially prior to the first consumption of food by subjects in the TRF group. The following analyzes will be measured in plasma samples: ketones, fasting glucose, fasting insulin, hemoglobin A1c, liver function, renal function, albumin, lipid profiles, MMP-9, IL-6, TNF-alpha, exosome markers (phospho-IRS1, phospho-Tau, Abeta1-42). Metabolomic and lipidomic analyses will be performed on the baseline and 3-month time point plasma samples.

Primary Outcome Measures

Name	Time	Method
The events of stroke in-evolution, stroke recurrence and hypoglycemia in acute ischemic stroke patients with time restricted fasting (TRF) or normal eating (NE)	4 weeks	1. Stroke in-evolution is defined as an increase in the NIHSS score of ≥2 points compared to initial score or the lowest score during admission, excluding other attributable medical or systemic causes. 2. Stroke recurrence is defined as newly developed neurological deficit due to acute cerebrovascular insult during the study period. 3. Hypoglycemia event is defined as symptomatic hypoglycemia fulfilling the criteria of Whipple's triad as symptoms known or likely to be caused by hypoglycemia, a low plasma glucose (\< 60 mg/dl) measured at the time of the symptoms and relief of symptoms when the glucose is raised to normal

Secondary Outcome Measures

Name	Time	Method
3 months functional outcome, defined as modified Rankin Scale (mRS) <=1 as good outcome	3 months	Good functional outcome defined as modified Rankin Scale \<=1.
Diffusion tensor imaging on MRI at baseline and 3 months post stroke	3 months	To evaluate the changes of diffusion tensor imaging on MRI at 3 months post stroke in TRF compared to baseline and NE in acute ischemic stroke patients.