The Effects of Acupuncture on the Risk of AD After TBI

The Effects of Acupuncture on the Risk of AD After TBI: A Randomized Controlled Trial

Traumatic brain injury (TBI) is a severely disabling injury which affects 150-200 people per million annually. Increasing evidence suggests that TBI may be a major risk of dementia, Alzheimer's disease (AD) in particular. Postmortem evidence has shown that beta-amyloid (Aβ) deposits, one of the most validated pathological biomarkers of AD, are present in the brains of severe TBI patients. Although the underlying mechanisms remain unclear, the axonal injury may play a role. Imaging investigations have revealed Aβ density maps of TBI patients overlapped with those of AD patients, and increased Aβdensity not only associated with prolonged TBI duration but also associated with decreased white matter integrity. Hence, the increasing accumulation in Aβ due to TBI may contribute to the initiation of the pathological alterations seen in AD. Treatment of TBI may not only be of benefit for the injury itself but also act to block the pathological changes in AD.

As a part of the clinical arm of the project, in this subproject investigators will conduct a single-blind, block-randomized clinical trial to investigate the efficacy of acupuncture in TBI. More specifically, investigators hypothesize that acupuncture intervention will elicit neuroprotective processes and thereby reduce axonal damage in TBI, manifested as (1) decreased plasma levels of Aβ peptide, tau, and glial fibrillary acidic protein (GFAP) and (2) increased white matter integrity after acupuncture. Ninety-six participants will be randomly allocated to the acupuncture intervention (verum acupuncture) or control group (sham acupuncture) in a 1:1 ratio. All participants will receive 20 minutes of acupuncture treatment twice a week for 2 weeks. A set of commonly used acupoints for TBI treatment will be manually stimulated every 10 minutes. The multi-modality magnetic resonance imaging (T1, T2, and diffusion tensor imaging) and blood sample will be taken before and after the acupuncture session to measure the white matter integrity in brain and plasma levels of Aβ peptide, tau, and GFAP, respectively. After integrate these data with other subprojects, we can provide synergic and integrative mechanisms of the effects of acupuncture on the risk of AD after TBI.

Study Overview

• Status: Unknown
• Conditions: Brain Injuries, Traumatic
• Intervention / Treatment: Procedure: Acupuncture

• Study Type: Interventional
• Enrollment (Anticipated): 76
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Taiwan
  • Taichung, Taiwan, 404
    • Recruiting
    • China Medical University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. age ≥ 20 years old
2. GCS score > 13
3. LOC < 30 minutes
4. hospital admission < 7 days
5. having adequate competency for understanding the study and a willingness to sign the written informed consent forms
6. be able to commence the acupuncture intervention within 2 weeks after TBI diagnosis

Exclusion Criteria:

1. medical history of neurological, cardiovascular events, or mental disorder, e.g., epilepsy, stroke, major depression or anxiety
2. other major medical conditions, e.g., active cancer, uncontrolled diabetes, pregnancy
3. surgery for TBI
4. receipt of acupuncture within the 6 months prior to study entry
5. patients with pacemaker, metal graft, or claustrophobia
6. preparing for pregnancy during the trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Acupuncture group; Disposable acupuncture needles will be inserted into acupoints for a depth of 10-30 mm in a direction oblique or parallel to the surface. To ensure allocation concealment, all needles will be affixed with plastic O-rings and adhesive tapes.	Procedure: Acupuncture; 20 minutes of acupuncture treatment, twice a week for 2 weeks. Acupoints will be manually stimulated every 10 minutes.
SHAM_COMPARATOR: Control group; Streitberger's non-invasive placebo acupuncture needles will be used in the control group; blunt-tipped needles will touch the skin quickly without being inserted. To ensure allocation concealment, all needles will be affixed with plastic O-rings and adhesive tapes.	Procedure: Acupuncture; 20 minutes of acupuncture treatment, twice a week for 2 weeks. Acupoints will be manually stimulated every 10 minutes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Decreased plasma levels of Aβ peptide	After 2-week acupuncture treatment interval
Decreased plasma levels of tau	After 2-week acupuncture treatment interval
Decreased plasma levels of glial fibrillary acidic protein (GFAP)	After 2-week acupuncture treatment interval

Secondary Outcome Measures

Outcome Measure	Time Frame
Increased white matter integrity	After 2-week acupuncture treatment interval

Collaborators and Investigators

• Sponsor: China Medical University Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 25, 2017
• Primary Completion (ANTICIPATED): June 1, 2020
• Study Completion (ANTICIPATED): June 1, 2020

Study Registration Dates

• First Submitted: December 8, 2017
• First Submitted That Met QC Criteria: December 17, 2017
• First Posted (ACTUAL): December 19, 2017

Study Record Updates

• Last Update Posted (ACTUAL): March 8, 2018
• Last Update Submitted That Met QC Criteria: March 6, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: Alzheimer's disease; Magnetic resonance imaging; Brain Injuries, Traumatic; white matter integrity; beta-Amyloid
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Craniocerebral Trauma; Trauma, Nervous System; Brain Injuries; Brain Injuries, Traumatic
• Other Study ID Numbers: CMUH106-REC2-139

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No