Metabolic Abnormalities and Intestinal Microecology in Patients With Chronic Disorders of Consciousness

Following severe traumatic brain injury, patients may remain unconscious for many years. It is the intestinal microbiome and metabolomics analysis comparing differentially intestinal microflora and metabolites between patients with chronic disorder of consciousness and controls so far. The investigators have mature data analysis technology. The obtained results provide new insight into understanding the molecular mechanisms underlying the chronic disorder of consciousness

Study Overview

• Status: Completed
• Conditions: Disorder of Consciousness
• Intervention / Treatment: Other: No intervention

Detailed Description

Objective:To determine differences in metabolic profiles and Intestinal microbial abundance among healthy human individuals and patients in a vegetative state (VS) and minimally conscious state (MCS) and to identify metabolites in human plasma that can accurately distinguish VS patients from MCS patients.

Method: Plasma samples and fecal sample were obtained from patients with chronic disorder of consciousness, and healthy volunteers. A comprehensive metabolic profile was obtained with targeted metabolomics analysis and untargeted and targeted lipidomics analysis, as well as intestinal microbial abundance from 16S rRNA gene amplicon sequencing.

• Study Type: Observational
• Enrollment (Actual): 200

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310002
      • SCIEX QTRAP 5500 liquid chromatograph / triple quadrupole mass spectrometer.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Patients with chronic disorder of consciousness were recruited at the rehabilitation units of Hangzhou Hospital of Zhejiang Armed Police Corps, China and Hangzhou Mingzhou Brain Rehabilitation Hospital.

Description

Inclusion Criteria:

1. Patients ages 18 to 80 years old;
2. Patients had a history of severe Traumatic brain injury (TBI);
3. Patients had awakened from a coma (indicating preserved sleep-wake cycles), including vegetative state and minimally consciousness state;
4. Patients stay unconscious for more than 1 month.

Exclusion Criteria:

1. Patients with disorders of consciousness caused by other inducements;
2. Other neurological or psychiatric conditions prior to the current brain injury;
3. Persistent seizure-like activity, inhibition or seizure inhibition;
4. The patients had taken a sedative barbiturate neuroleptics or antidepressants within one month;
5. The clinical state is unstable, and there are signs of spontaneous recovery or deterioration within 1 week;
6. The patients have taken gastrointestinal motility drugs or other drugs affecting gastrointestinal motility in the past month;
7. Had taken antibiotics and probiotics in the past month;
8. Patients with intestinal diseases such as colon cancer, ulcerative colitis or crohn's disease;
9. Patients with acute infectious diseases or liver dysfunction

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Emerged from Minimally Conscious State (EMCS); Emerged from Minimally Conscious State (EMCS): recovery of functional object uses or communication from chronic	Other: No intervention; No intervention
Minimally conscious state (MCS); Minimally conscious state (MCS): have reproducible signs of awareness and exhibit fluctuations in consciousness	Other: No intervention; No intervention
Vegetative state (VS); Vegetative state (VS): can open their eyes and preserve sleep-wake cycles, but unaware of themselves and their surroundings	Other: No intervention; No intervention
Healthy controls (HCs)	Other: No intervention; No intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
metabolic profiling and Intestinal microbial spectrum	A comprehensive metabolic profile from plasma was obtained with targeted metabolomics analysis and untargeted and targeted lipidomics analysis; intestinal microbial spectrum was obetained from fecal by16S rRNA gene sequencing among HCs, EMCS, MCS and VS groups.	1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Coma Recovery Scale-Revised(CRS-R)	Coma Recovery Scale-Revised (CRS-R) score was used to quantify the severity, which consists of 23 hierarchically arranged items that comprise six subscales addressing auditory, visual, motor, oromotor/verbal, communication, and arousal processes. The lowest item on each subscale represents reflexive activity, whereas the highest items represent cognitively mediated behaviors In total, The lowest mark on the scale is 0 and the highest mark is 23. To a certain extent, the higher the score is, the better the level of consciousness is, whereas the lower the level of consciousness is.	30 minutes before samples collection
Glasgow Outcome Scale (GOS)	A GOS value of <3 was considered as a bad recovery, while a GOS value of ≥3 was considered as a good recovery.	6 months
Indicators of brain connectivity by EEG	Phase locking value (PLV)	On the same day as collecting the samples

Collaborators and Investigators

• Sponsor: First Affiliated Hospital of Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): March 13, 2018
• Primary Completion (Actual): September 1, 2022
• Study Completion (Actual): April 1, 2023

Study Registration Dates

• First Submitted: July 29, 2020
• First Submitted That Met QC Criteria: August 27, 2020
• First Posted (Actual): August 28, 2020

Study Record Updates

• Last Update Posted (Actual): May 7, 2024
• Last Update Submitted That Met QC Criteria: May 6, 2024
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: microbiome; metabolomics; Disorder of Consciousness
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Neurocognitive Disorders; Disease Attributes; Chronic Disease; Consciousness Disorders
• Other Study ID Numbers: microbiome and metabolomic

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