Clinical trial NCT03944993: Effects of Pulsed Electromagnetic Fields (PEMFS) On Cerebral Haemodynamics
Official title: Effects of Pulsed Electromagnetic Fields (PEMFS) On Cerebral Haemodynamics - EPOCH Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Cerebral Hemodynamics
Cognitive Change
Keywords: PEMF
Prefrontal cortex
Exercise mimetic
Pulsed Electromagnetic Fields
Lead sponsor: National University Hospital, Singapore
Sponsor class: OTHER
Collaborators: name: National University of Singapore
First posted: 2019-05-10
Enrollment: 6
Sex: ALL
Minimum age (years): 21
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The study is designed as a double-blinded, randomised, controlled pilot study. As a pilot study, 33 healthy adults will be enrolled and randomised into the intervention or sham arm at 2:1 ratio. Within the intervention arm, 50% of the participants will receive PEMFs in the non-dominant leg and the remaining 50% will receive intervention in the dominant leg (n = 11, 11). There are no restrictions based on race or gender.
Primary purpose: TREATMENT

Brief summary: The investigators are looking to determine the effects of PEMFs device on cerebral blood flow and cognition in healthy volunteers. Through in vitro tests and in vivo animal studies, the investigators have shown that at an extremely low flux density (strength) of 1 millitesla (mT) and with short exposures of 10 minutes a week, PEMFs can recapitulate many of the healthful benefits of exercise without imparting a mechanical stress on the tissues and cells.

In the first-in-man study, 10 healthy volunteers were exposed to PEMFs for 6 weeks with 10 minutes of field exposure per week, and experienced an average increase of 30% in leg strength. No side effects were reported.

In this study, the investigators aim to understand the cerebral effects of an exercise mimetic (PEMFs) via the muscle milieu.

Detailed description: Human and animal studies have reported the beneficial influence of exercise on cognitive and brain functions. Accordingly, exercise is drawing increasing research attention as a possible lifestyle factor for improving neurocognitive functions.

Low frequency and low amplitude Pulsed Electromagnetic Fields (PEMFs) recapitulate many of the benefits of exercise by activating many of the same cellular second messenger cascades activated by mechanical input (exercise) yet, without imparting a physical stress on the cells. Through a series of in vitro and in vivo experiments the investigators have shown that at field strengths of 1-2 mT amplitude, the PEMF system stimulates muscle without physically stressing the tissues and delivers the following benefits: 1) slows muscle loss, 2) improves muscle strength and, 3) releases important regenerative and metabolism-enhancing agents.

Functional near-infrared spectroscopy (fNIRS) is a relatively new optical imaging technology that uses light in the near-infrared spectrum to non-invasively monitor the haemodynamic responses evoked by neural activity through measuring the changes in oxyhaemoglobin (HbO) and deoxyhaemoglobin (HbR) concentrations in the cerebral cortex. The increased blood supply to the area of neural activation typically results in an increase in HbO concentration while a decrease is observed in HbR due to the blood's washout effect. The HbO and HbR responses from fNIRS measurements have been shown to be spatially and temporally correlated with the blood oxygen level-dependent signal obtained by fMRI. The advantage of fNIRS over other imaging modalities is that it is inexpensive, non-invasive, non-ionising and portable, making it a highly popular modality for implementing brain-computer interfaces. OBELAB NIRSIT is a commercially available, high-density fNIRS device that optically measures haemodynamic variations in the pre-frontal cortex (PFC).

Low-frequency and low amplitude pulsed electromagnetic fields (PEMFs) recapitulate many of the healthful benefits of exercise by activating many of the same cellular second messenger cascades activated by mechanical input (exercise) yet, without imparting a physical stress on the cells. Response windows are a largely unrecognised rule in mechanobiological systems, whereby cells are most responsive to a given strain, duration and frequency of stimulation; greater strain of higher frequency and duration of stimulation is too much of a stress for cells and results in null responses.

The investigators have shown that PEMFs likewise obey an electromagnetic window of efficacy with temporal and frequency dependencies of similar scale as those required for mechanical stimulation, further supporting the conclusion that PEMFs are activating cellular mechanotransduction pathways. At field strengths of 1-2 mT amplitude, the PEMF system stimulates muscle without physically stressing the tissues and aims to deliver the following benefits: 1) slows muscle loss; 2) improves muscle strength and; 3) releases important regenerative and metabolism-enhancing agents. Accordingly, this study will investigate the exercise mimetic effects of PEMFs on cerebral haemodynamics and cognitive performance via targeting muscle. The results of this study will support future work with patients with memory deficits, such as mild cognitive impairment, to possibly mitigate disease progression.

Eligibility criteria: Inclusion Criteria:

* Age between 21- 65 years
* Ability to provide informed consent

Exclusion Criteria:

* Received any investigational drug or device within 30 days prior to study baseline visit or is enrolled in another clinical trial
* History of cardiac, neurological, or rheumatic diseases
* History of malignancy within the past 5 years
* Undergone surgery of any type within the past 6 months
* Anticipated need for surgery of any type during the next 3 months
* Previous treatment with the study device
* Metal implants in the lower limb
* Existing or planned pregnancy
* Lactating women
* Leg circumference \> 63 cm
* Colour vision deficiency

Primary outcomes:
measure: Change in cerebral haemodynamic responses
timeFrame: Baseline and Week 7
measure: Change in cognitive performance
timeFrame: Baseline and Week 7
Secondary outcomes:
measure: Quadriceps muscle strength
timeFrame: Baseline and Week 7
measure: Thigh girth
timeFrame: Baseline and Week 7
Other outcomes:
Locations:
city: Singapore
country: Singapore
facility: National University Hospital
Study officials:
affiliation: National University of Singapore
name: Alfredo Franco-Obregon
role: PRINCIPAL_INVESTIGATOR
References:
citation: Parate D, Franco-Obregon A, Frohlich J, Beyer C, Abbas AA, Kamarul T, Hui JHP, Yang Z. Enhancement of mesenchymal stem cell chondrogenesis with short-term low intensity pulsed electromagnetic fields. Sci Rep. 2017 Aug 25;7(1):9421. doi: 10.1038/s41598-017-09892-w.
citation: Crocetti S, Beyer C, Schade G, Egli M, Frohlich J, Franco-Obregon A. Low intensity and frequency pulsed electromagnetic fields selectively impair breast cancer cell viability. PLoS One. 2013 Sep 11;8(9):e72944. doi: 10.1371/journal.pone.0072944. eCollection 2013.