HealthyNCT05252247
The Effects of Immobilisation and Exercise on Homeostatic Plasticity Mechanisms in Healthy Participants
A study testing Immobilisation and Exercise in people with Healthy, run by Aalborg University at 1 site in Denmark.
Trial summary
Homeostasis is important for maintaining a stable equilibrium of e.g., blood pressure, hormonal release, and release of neurotransmitters. Within the healthy brain, homeostatic plasticity mechanisms ensure stability in synaptic plasticity that maintains cortical excitability within a normal physiological range, while… Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Immobilisation and Exercise
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteDenmark
- Study dates
- 15 Feb 2022to 31 Dec 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- o Healthy, aged between 18-60 years, right-handed, and can speak, read, and understand Danish or English
Who cannot join
- Pregnant or breastfeeding
- Regular use of cannabis, opioids or other drugs (except contraceptives)
- Current or previous neurologic, musculoskeletal, mental, or other illnesses (e.g. brain or spinal cord injuries, degenerative neurological disorders, epilepsy, major depression, cardiovascular disease, chronic lung disease, etc.)
- Current or previous chronic or recurrent pain condition
- Current regular use of analgesic medication or other medication which may affect the trial (including paracetamol and NSAIDs)
- Lack of ability to cooperate
Show all 11Show fewer
- Recent history of acute pain particularly in the lower limbs (unless related to low back pain in patients included in sub-project 6)
- Abnormally disrupted sleep in 24 hours preceding experiment
- Any medical or other condition (i.e. musculoskeletal, cardiorespiratory, neurological, etc.)
- Contraindications to TMS application (history of epilepsy, metal implants in head or jaw, etc.)
- Unable to pass the "Transcranial Magnetic Stimulation Adult Safety Screen" or tDCS screening questionnaire
Trial locations and contacts
1 site in 1 country.
About this study
Homeostasis is important for maintaining a stable equilibrium of e.g., blood pressure, hormonal release, and release of neurotransmitters. Within the healthy brain, homeostatic plasticity mechanisms ensure stability in synaptic plasticity that maintains cortical excitability within a normal physiological range, while this regulation has been shown to be impaired in chronic pain conditions such as low back pain. Cortical excitability can also be decreased and increased experimentally, using immobilisation and exercise paradigms, respectively, yet it is unknown if this overall change in excitability is caused by a shift in homeostatic plasticity regulation. Investigating if immobilisation and exercise influences homeostatic plasticity responses, may therefore reveal important information on the malleability of homeostatic plasticity mechanisms and ways to modulate them.
Read the detailed description
The aim of this study is to investigate the impact of upper limb immobilisation and physical exercise of the hand on homeostatic plasticity in healthy individuals.
The study will be performed as a randomised cross-over study where each participant take part in three sessions, separated by approximately 24 hours. During each session, the participant will answer questionnaires and undergo quantitative sensory testing (QST). Baseline measures is obtained using transcranial magnetic stimulation (TMS)-induced motor evoked potentials (MEPs), which is done before the induction of homeostatic plasticity using transcranial direct current stimulation (tDCS). MEPs are then obtained every 10 minutes for 30 minutes. Lastly, QST measures are obtained again.
As no previous studies have investigated the effect of immobilisation and exercise on homeostatic plasticity response, a sample size calculation was estimated based on MEP analysis from a previous study using α of 0.05, β of 0.80, and effect size of 0.29, yielding 22 participants. This is consistent with recent exploratory research that suggested that up to 28 participants would be needed. Therefore, the current study aimed at including 28 participants with an interim analysis performed after 10-15 inclusions.
Each participant will attend three identical experimental sessions on the same time on three consecutive days. Eight hours before attending the experimental sessions with immobilisation the participant will be fitted a splint (MANU-Hit DIGITUS POLLEX, Clinical Innovations, DK) to immobilise the right hand. Similarly, eight hours before attending the exercise session, the participant will be instructed to perform 150 ballistic finger movements with a pace of 0.5 Hz. During the experiment, the participant will be seated comfortably with arms and hands at rest. Electromyography electrodes will be placed on the right first interosseous muscle to assess the corticomotor excitability by recording of TMS induced MEPs on the left primary motor cortex. A neoprene cap will then be mounted to the head, and the optimal site for TMS (hotspot) will be identified and marked on the cap for standardisation. The cortical excitability will be measured before and immediately after homeostatic plasticity induction (time point 0-min), and then every 10 minutes for 30 minutes.
Homeostatic plasticity will be induced using tDCS applied to the left primary motor cortex for 7 minutes, followed by a break of 3 minutes and another 5 minutes of tDCS. A constant current of 1mA will be transmitted through the tDCS system (Starstim 32, Neuroelectrics, Barcelona, Spain) using two gelled electrodes placed into holes of a neoprene cap at the position of C3 and Fp2.
The distribution of the data will be tested using a Shapiro-Wilk's test of normality. To investigate the effect of immobilisation and exercise on homeostatic plasticity, a two-way repeated measures analysis of variance (RM-ANOVA) will be conducted with factors Session (Session 1, session 2, and session 3) and Time (baseline, 0 min, 10 min, 20min, and 30 min) and a P value of <0.05 will be considered statistically significant. Adjustments will be made for multiple post-hoc comparisons using appropriate corrections.
- Conditions
- Healthy
- Being tested
- Immobilisation, Exercise
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ImmobilisationOther
Eight hours prior to attending the immobilisation session, a splint will be fitted to the hand of the participant and remain until the session start.
ExerciseOther
Eight hours prior to attending the exercise session, the participant will be instructed to perform 150 ballistic finger movements every hour until the session start.
| Study group | Role | What they receive |
|---|---|---|
| Conditions | Experimental | Participants will attend three sessions where two consist of immobilisation or exercise interventions. Receives: Other: Immobilisation; Other: Exercise |
What is being measured
The primary outcome is the main question the study is designed to answer.
Corticospinal excitability
Change in corticospinal excitability (compared to baseline), as reflected by motor-evoked potential amplitudes induced by transcranial magnetic stimulation, after homeostatic plasticity induction
Measured: Immediately after [0 minutes after homeostatic plasticity induction] and every 10 minutes up until 30 minutes after [10-30 minutes after homeostatic plasticity induction]
Secondary outcomes (12)
Quantitative Sensory Testing: Cuff detection threshold
Cuff detection threshold [kPa]
Measured: Before and 30 minutes post homeostatic plasticity induction
Quantitative Sensory Testing: Cuff pain tolerance threshold
Cuff pain tolerance threshold [kPa]
Measured: Before and 30 minutes post homeostatic plasticity induction
Quantitative Sensory Testing: Conditioned pain modulation
Conditioned pain modulation [kPa change]
Measured: Before and 30 minutes post homeostatic plasticity induction
Quantitative Sensory Testing: Temporal summation of pain
Temporal summation of pain [pain rating; Visual analogue scale; 0-10 cm; higher scores means more pain]
Measured: Before and 30 minutes post homeostatic plasticity induction
Quantitative Sensory Testing: Mechanical pain threshold
Mechanical pain threshold (pin prick) [force required for inducing pricking pain; nM]
Measured: Before and 30 minutes post homeostatic plasticity induction
Quantitative Sensory Testing: Handheld algometry at right dorsal interosseous muscle
Handheld algometry at right dorsal interosseous muscle [kPa]
Measured: Before and 30 minutes post homeostatic plasticity induction
Quantitative Sensory Testing: Handheld algometry at left dorsal interosseous muscle
Handheld algometry at left dorsal interosseous muscle [kPa]
Measured: Before and 30 minutes post homeostatic plasticity induction
Quantitative Sensory Testing: Handheld algometry at right tibialis anterior muscle
Handheld algometry at right tibialis anterior muscle [kPa]
Measured: Before and 30 minutes post homeostatic plasticity induction
Questionnaires: Pittsburgh Sleep Quality Index
Pittsburgh Sleep Quality Index (PSQI; 0-21; PSQI > 5 means poor sleep quality)
Measured: Before baseline corticospinal excitability measurements
Questionnaires: Pain Catastrophizing Scale
Pain Catastrophizing Scale (PCS; 0-52; higher score means more pain catastrophizing)
Measured: Before baseline corticospinal excitability measurements
Questionnaires: International Physical Activity Questionnaire
International Physical Activity Questionnaire (IPAQ; resting metabolic rate multiplied by activity per minutes performed > higher means better physical activity)
Measured: Before baseline corticospinal excitability measurements
Questionnaires: Positive and Negative Affective Schedule
Positive and Negative Affective Schedule - Short Form (PANAS; 10-50; higher scores = higher levels of negative or positive affect)
Measured: Before baseline corticospinal excitability measurements
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Feb 2022
- Study start15 Feb 2022
- Primary completion31 Dec 2022
- Study completion31 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for HealthyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This is a within-subject repeated measures comparisons study with one baseline session and two interventional sessions.
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aalborg University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dennis Boye Larsen, Aalborg University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05252247
- Sponsor's protocol ID
- N-20210047
- Status last verified
- Feb 2023
- First submitted
- 19 Jan 2022
- Last updated
- 6 Feb 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Fricke K, Seeber AA, Thirugnanasambandam N, Paulus W, Nitsche MA, Rothwell JC. Time course of the induction of homeostatic plasticity generated by repeated transcranial direct current stimulation of the human motor cortex. J Neurophysiol. 2011 Mar;105(3):1141-9. doi: 10.1152/jn.00608.2009. Epub 2010 Dec 22.
PubMed 21177994Thapa T, Graven-Nielsen T, Chipchase LS, Schabrun SM. Disruption of cortical synaptic homeostasis in individuals with chronic low back pain. Clin Neurophysiol. 2018 May;129(5):1090-1096. doi: 10.1016/j.clinph.2018.01.060. Epub 2018 Feb 9.
PubMed 29472134Thapa T, Graven-Nielsen T, Schabrun SM. Aberrant plasticity in musculoskeletal pain: a failure of homeostatic control? Exp Brain Res. 2021 Apr;239(4):1317-1326. doi: 10.1007/s00221-021-06062-3. Epub 2021 Feb 26.
PubMed 33635391Wittkopf PG, Larsen DB, Gregoret L, Graven-Nielsen T. Prolonged corticomotor homeostatic plasticity - Effects of different protocols and their reliability. Brain Stimul. 2021 Mar-Apr;14(2):327-329. doi: 10.1016/j.brs.2021.01.017. Epub 2021 Jan 24. No abstract available.
PubMed 33503491
Study at a glance
From the registry record, last updated by the sponsor on 6 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of Immobilisation and Exercise on Homeostatic Plasticity Mechanisms in Healthy Participants
- ClinicalTrials.gov ID
- NCT05252247
- Acronym / sponsor ID
- N-20210047
- Conditions
- Healthy
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Aalborg UniversityUniversity, hospital or other
- Study start
- 15 Feb 2022 (actual)
- Primary completion
- 31 Dec 2022 (actual)
- Study completion
- 31 Dec 2022 (actual)
- First posted
- 23 Feb 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Homeostasis is important for maintaining a stable equilibrium of e.g., blood pressure, hormonal release, and release of neurotransmitters. Within the healthy brain, homeostatic plasticity mechanisms ensure stability in synaptic plasticity that maintains cortical excitability within a normal physiological range, while this regulation has been shown to be impaired in chronic pain conditions such as low back pain. Cortical excitability can also be decreased and increased experimentally, using immobilisation and exercise paradigms, respectively, yet it is unknown if this overall change in excitability is caused by a shift in homeostatic plasticity regulation. Investigating if immobilisation and exercise influences homeostatic plasticity responses, may therefore reveal important information on the malleability of homeostatic plasticity mechanisms and ways to modulate them.
Detailed description
The aim of this study is to investigate the impact of upper limb immobilisation and physical exercise of the hand on homeostatic plasticity in healthy individuals.
The study will be performed as a randomised cross-over study where each participant take part in three sessions, separated by approximately 24 hours. During each session, the participant will answer questionnaires and undergo quantitative sensory testing (QST). Baseline measures is obtained using transcranial magnetic stimulation (TMS)-induced motor evoked potentials (MEPs), which is done before the induction of homeostatic plasticity using transcranial direct current stimulation (tDCS). MEPs are then obtained every 10 minutes for 30 minutes. Lastly, QST measures are obtained again.
As no previous studies have investigated the effect of immobilisation and exercise on homeostatic plasticity response, a sample size calculation was estimated based on MEP analysis from a previous study using α of 0.05, β of 0.80, and effect size of 0.29, yielding 22 participants. This is consistent with recent exploratory research that suggested that up to 28 participants would be needed. Therefore, the current study aimed at including 28 participants with an interim analysis performed after 10-15 inclusions.
Each participant will attend three identical experimental sessions on the same time on three consecutive days. Eight hours before attending the experimental sessions with immobilisation the participant will be fitted a splint (MANU-Hit DIGITUS POLLEX, Clinical Innovations, DK) to immobilise the right hand. Similarly, eight hours before attending the exercise session, the participant will be instructed to perform 150 ballistic finger movements with a pace of 0.5 Hz. During the experiment, the participant will be seated comfortably with arms and hands at rest. Electromyography electrodes will be placed on the right first interosseous muscle to assess the corticomotor excitability by recording of TMS induced MEPs on the left primary motor cortex. A neoprene cap will then be mounted to the head, and the optimal site for TMS (hotspot) will be identified and marked on the cap for standardisation. The cortical excitability will be measured before and immediately after homeostatic plasticity induction (time point 0-min), and then every 10 minutes for 30 minutes.
Homeostatic plasticity will be induced using tDCS applied to the left primary motor cortex for 7 minutes, followed by a break of 3 minutes and another 5 minutes of tDCS. A constant current of 1mA will be transmitted through the tDCS system (Starstim 32, Neuroelectrics, Barcelona, Spain) using two gelled electrodes placed into holes of a neoprene cap at the position of C3 and Fp2.
The distribution of the data will be tested using a Shapiro-Wilk's test of normality. To investigate the effect of immobilisation and exercise on homeostatic plasticity, a two-way repeated measures analysis of variance (RM-ANOVA) will be conducted with factors Session (Session 1, session 2, and session 3) and Time (baseline, 0 min, 10 min, 20min, and 30 min) and a P value of <0.05 will be considered statistically significant. Adjustments will be made for multiple post-hoc comparisons using appropriate corrections.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is a within-subject repeated measures comparisons study with one baseline session and two interventional sessions.
| Arm | Type | Receives |
|---|---|---|
| Conditions | Experimental | Other: Immobilisation, Other: ExerciseParticipants will attend three sessions where two consist of immobilisation or exercise interventions. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- o Healthy, aged between 18-60 years, right-handed, and can speak, read, and understand Danish or English
Key exclusion criteria (11 listed)
- Pregnant or breastfeeding
- Regular use of cannabis, opioids or other drugs (except contraceptives)
- Current or previous neurologic, musculoskeletal, mental, or other illnesses (e.g. brain or spinal cord injuries, degenerative neurological disorders, epilepsy, major depression, cardiovascular disease, chronic lung disease, etc.)
- Current or previous chronic or recurrent pain condition
- Current regular use of analgesic medication or other medication which may affect the trial (including paracetamol and NSAIDs)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ImmobilisationEight hours prior to attending the immobilisation session, a splint will be fitted to the hand of the participant and remain until the session start. | Other | Conditions |
| ExerciseEight hours prior to attending the exercise session, the participant will be instructed to perform 150 ballistic finger movements every hour until the session start. | Other | Conditions |
Primary outcome
Corticospinal excitability
Time frame: Immediately after [0 minutes after homeostatic plasticity induction] and every 10 minutes up until 30 minutes after [10-30 minutes after homeostatic plasticity induction]
Change in corticospinal excitability (compared to baseline), as reflected by motor-evoked potential amplitudes induced by transcranial magnetic stimulation, after homeostatic plasticity induction
12 secondary outcomes
Quantitative Sensory Testing: Cuff detection threshold
Time frame: Before and 30 minutes post homeostatic plasticity induction
Quantitative Sensory Testing: Cuff pain tolerance threshold
Time frame: Before and 30 minutes post homeostatic plasticity induction
Quantitative Sensory Testing: Conditioned pain modulation
Time frame: Before and 30 minutes post homeostatic plasticity induction
Quantitative Sensory Testing: Temporal summation of pain
Time frame: Before and 30 minutes post homeostatic plasticity induction
Quantitative Sensory Testing: Mechanical pain threshold
Time frame: Before and 30 minutes post homeostatic plasticity induction
Quantitative Sensory Testing: Handheld algometry at right dorsal interosseous muscle
Time frame: Before and 30 minutes post homeostatic plasticity induction
Quantitative Sensory Testing: Handheld algometry at left dorsal interosseous muscle
Time frame: Before and 30 minutes post homeostatic plasticity induction
Quantitative Sensory Testing: Handheld algometry at right tibialis anterior muscle
Time frame: Before and 30 minutes post homeostatic plasticity induction
Questionnaires: Pittsburgh Sleep Quality Index
Time frame: Before baseline corticospinal excitability measurements
Questionnaires: Pain Catastrophizing Scale
Time frame: Before baseline corticospinal excitability measurements
Questionnaires: International Physical Activity Questionnaire
Time frame: Before baseline corticospinal excitability measurements
Questionnaires: Positive and Negative Affective Schedule
Time frame: Before baseline corticospinal excitability measurements
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Feb 2023.
- Background: PubMed 21177994Fricke K, Seeber AA, Thirugnanasambandam N, Paulus W, Nitsche MA, Rothwell JC. Time course of the induction of homeostatic plasticity generated by repeated transcranial direct current stimulation of the human motor cortex. J Neurophysiol. 2011 Mar;105(3):1141-9. doi: 10.1152/jn.00608.2009. Epub 2010 Dec 22.
- Background: PubMed 29472134Thapa T, Graven-Nielsen T, Chipchase LS, Schabrun SM. Disruption of cortical synaptic homeostasis in individuals with chronic low back pain. Clin Neurophysiol. 2018 May;129(5):1090-1096. doi: 10.1016/j.clinph.2018.01.060. Epub 2018 Feb 9.
- Background: PubMed 33635391Thapa T, Graven-Nielsen T, Schabrun SM. Aberrant plasticity in musculoskeletal pain: a failure of homeostatic control? Exp Brain Res. 2021 Apr;239(4):1317-1326. doi: 10.1007/s00221-021-06062-3. Epub 2021 Feb 26.
- Background: PubMed 33503491Wittkopf PG, Larsen DB, Gregoret L, Graven-Nielsen T. Prolonged corticomotor homeostatic plasticity - Effects of different protocols and their reliability. Brain Stimul. 2021 Mar-Apr;14(2):327-329. doi: 10.1016/j.brs.2021.01.017. Epub 2021 Jan 24. No abstract available.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Immobilisation and Exercise in people with Healthy, run by Aalborg University at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Corticospinal excitability (time frame: Immediately after [0 minutes after homeostatic plasticity induction] and every 10 minutes up until 30 minutes after [10-30 minutes after homeostatic plasticity induction]). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05252247, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Feb 2023.