Neck PainNCT05568394
Effects of Manual Therapy Combined With Therapeutic Exercise on Brain Biomarkers in Neck Pain
A study testing Manual therapy combinded with therapeutic exercise and Routine physical therapy in people with Neck Pain, run by Chiang Mai University at 1 site in Thailand.
Trial summary
Structural brain alterations in pain-related areas have been demonstrated in patients with nonspecific neck pain. While manual therapy combined with therapeutic exercise is an effective management for neck pain, its underlying mechanisms are poorly understood. Read more about this study
- Who is it for?
- Ages 18 to 59 years
- Conditions the study is for
- Neck Pain
- What is being tested?
- Manual therapy combinded with therapeutic exercise and Routine physical therapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 52 participants
- Where
- 1 siteThailand
- Study dates
- 15 Nov 2022to 5 Feb 2024
- 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 59 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- a history of nonspecific neck pain for ≥ 3 months
- an average pain intensity over the past week ≥ 35 mm. on a visual analogue scale (VAS)
Who cannot join
- a history of head and neck injury or surgery
- known or suspected vestibular pathology or dizziness caused by underlying pathology in the ear, brain and sensory nerve pathways (e.g. benign paroxysmal positional vertigo) and/or vascular disorders
- any neurological or musculoskeletal condition that could affect the outcomes (e.g., scoliosis, torticollis, myofascial pain syndrome, fibromyalgia and rheumatoid arthritis)
- metabolic conditions (e.g., diabetes, obesity (BMI > 30 kg/m2) and hypertension)
- psychological symptoms (e.g., anxiety, depression and schizophrenia)
- contraindications to MRI (e.g., pregnancy/breastfeeding, claustrophobia and ferromagnetic implants)
- receiving physiotherapy treatment for their neck conditions in the past 12 months.
Trial locations and contacts
1 site in 1 country.
Thailand1 site
Department of Physical Therapy, Faculty of Associated Medical Sciences
Chiang Mai, 50202
About this study
Official title: Effects of Manual Therapy Combined With Therapeutic Exercise on Brain Biomarkers in Patients With Chronic Nonspecific Neck Pain: Study Protocol for a Randomized Controlled Trial.
Structural brain alterations in pain-related areas have been demonstrated in patients with nonspecific neck pain. While manual therapy combined with therapeutic exercise is an effective management for neck pain, its underlying mechanisms are poorly understood. The primary objective of this trial is to investigate the effects of manual therapy combined with therapeutic exercise on brain imaging biomarkers in patients with chronic nonspecific neck pain. The secondary objectives are to assess neurochemical biomarkers, clinical features of neck pain, cervical range of motion and cervical muscle strength.
Read the detailed description
This study is a single-blinded, randomized controlled trial. Forty-eight participants with chronic nonspecific neck pain will be recruited into the study. Participants will be randomly allocated to either an intervention or control group (1:1 ratio). Participants in the intervention group will receive manual therapy combined with therapeutic exercise for 10 weeks (2 visits per week). The control group will receive routine physical therapy. Primary outcomes are brain imaging biomarkers (cortical gray matter: volume, thickness and area, and white matter: fractional anisotropy and mean diffusivity) in pain-related areas. Secondary outcomes are neurochemical biomarkers (N-acetylaspartate, NAA; creatine, Cr; glutamic acid/glutamine, Glu/Gln; myoinositol, mI; and choline, cho), clinical features (neck pain intensity, duration, neck disability and psychological symptoms), cervical range of motion and cervical muscle strength.
- Conditions
- Neck Pain
- Being tested
- Manual therapy combinded with therapeutic exercise, Routine physical therapy
- Keywords
- Neck pain, Manual therapy, Exercise, Magnetic resonance imaging, Magnetic resonance spectroscopy
- Medical subject headings
- Neck Pain, Motor Activity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Manual therapy combinded with therapeutic exerciseOther
The treatment includes cervical mobilization and specific therapeutic exercises: craniocervical and cervical flexors and extensors, axioscapular muscles, and postural correction (30-40 minutes).
The participants will attend 20 individual treatment sessions (2 visits per week for 10 weeks).
Routine physical therapyOther
The treatment includes routine physical therapy (e.g., modalities, range of motion and/or gentle stretching exercise) (30-40 minutes).
The participants will attend 20 individual treatment sessions (2 visits per week for 10 weeks).
| Study group | Role | What they receive |
|---|---|---|
| Intervention group | Experimental | Manual therapy and therapeutic exercise Receives: Other: Manual therapy combinded with therapeutic exercise |
| Control group | Experimental | Routine physical therapy Receives: Other: Routine physical therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cortical gray matter: volume and thickness
Cortical gray matter (volume and thickness) will be measured in pain-related areas (thalamus, prefrontal cortex (PFC), primary somatosensory cortex (S1), primary motor cortex (M1), insula, cingulate cortex, precuneus, temporal lobe and periaqueductal gray matter) using a Magnetic resonance imaging (MRI) machine
Measured: At baseline and post-intervention
Secondary outcomes (7)
Neurochemical biomarkers: N-acetylaspartate (NAA), creatine (Cr), glutamic acid/glutamine (Glu/Gln), myoinositol (mI), and choline (cho)
Neurochemistry biomarkers will be measured using single-voxel proton magnetic resonance spectroscopy (1H-MRS) in dorsolateral prefrontal cortex (DLPFC), primary somatosensory cortex (S1), anterior cingulate (ACC), insula and thalamus.
Measured: At baseline and post-intervention
Neck pain intensity
The average intensity of neck pain will be assessed by using a 0-10 cm visual analogue scale (VAS), with 0 indicating no pain and 10 indicating worst imaginable pain.
Measured: At baseline and post-intervention
Neck pain and disability
Neck Disability Index (NDI) will be used to assess how neck pain affects a patient's daily life and to assess the self-rated disability. A total score is 50, which a higher score indicates a higher disability.
Measured: At baseline and post-intervention
Anxiety and depression
The symptoms of anxiety and depression will be assessed using Hospital Anxiety and Depression Scale (HADS). It includes two subscales: anxiety (HADS-A) and depression (HADS-D). A total score for each subscale ranges from 0 to 21, with higher scores indicating worse symptoms.
Measured: At baseline and post-intervention
Cervical range of motion
Cervical range of motion (degrees) will be measured in flexion, extension, left-right lateral flexion and left-right rotation.
Measured: At baseline and post-intervention
Cervical muscle strength
Cervical muscle strength will be measured in a craniocervical flexion action, using a handheld dynamometer (Newtons).
Measured: At baseline and post-intervention
White matter integrity: fractional anisotropy (FA) and mean diffusivity (MD)
White matter in the brain will be quantified using diffusion tensor imaging (DTI) technique.
Measured: At baseline and post-intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Oct 2022
- Study start15 Nov 2022
- Primary completion28 Nov 2023
- Study completion5 Feb 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Neck PainStudies 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- A single-blinded design
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Lead sponsor
- Chiang Mai University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Sureeporn Uthaikhup, Chiang Mai University
- Investigators
- Sureeporn Uthaikhup, PhD., Principal investigator, Department of physical therapy, Chiang Mai university
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05568394
- Sponsor's protocol ID
- FF-65 2301484
- Status last verified
- Feb 2024
- First submitted
- 4 Oct 2022
- Last updated
- 7 Feb 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Jull G, Falla D, Treleaven J, O'Leary S. Management of neck pain disorders: a research informed approach. Edinburgh: Elseiver Limited; 2019.
Johnston V, O'Leary S, Comans T, Straker L, Melloh M, Khan A, Sjogaard G. A workplace exercise versus health promotion intervention to prevent and reduce the economic and personal burden of non-specific neck pain in office personnel: protocol of a cluster-randomised controlled trial. J Physiother. 2014 Dec;60(4):233; discussion 233. doi: 10.1016/j.jphys.2014.08.007. Epub 2014 Oct 11.
PubMed 25306220Sremakaew M, Jull G, Treleaven J, Barbero M, Falla D, Uthaikhup S. Effects of local treatment with and without sensorimotor and balance exercise in individuals with neck pain: protocol for a randomized controlled trial. BMC Musculoskelet Disord. 2018 Feb 13;19(1):48. doi: 10.1186/s12891-018-1964-3.
PubMed 29433500Maitland GD, Hengeveld E, Banks K, Anglaise K. Vertebral manipulation. 7th ed. Oxford: Butterworth-Heinemann: Elsevier; 2005.
de Zoete RMJ, Stanwell P, Weber KA, Snodgrass SJ. Differences in Structural Brain Characteristics Between Individuals with Chronic Nonspecific Neck Pain and Asymptomatic Controls: A Case-Control Study. J Pain Res. 2022 Feb 18;15:521-531. doi: 10.2147/JPR.S345365. eCollection 2022.
PubMed 35210851Coppieters I, De Pauw R, Caeyenberghs K, Lenoir D, DeBlaere K, Genbrugge E, Meeus M, Cagnie B. Differences in white matter structure and cortical thickness between patients with traumatic and idiopathic chronic neck pain: Associations with cognition and pain modulation? Hum Brain Mapp. 2018 Apr;39(4):1721-1742. doi: 10.1002/hbm.23947. Epub 2018 Jan 11.
PubMed 29327392Didehdar D, Kamali F, Yoosefinejad AK, Lotfi M. The effect of spinal manipulation on brain neurometabolites in chronic nonspecific low back pain patients: a randomized clinical trial. Ir J Med Sci. 2020 May;189(2):543-550. doi: 10.1007/s11845-019-02140-2. Epub 2019 Nov 26.
PubMed 31773541Chaikla R, Sremakaew M, Saekho S, Kothan S, Uthaikhup S. Effects of manual therapy combined with therapeutic exercise on brain structure in patients with chronic nonspecific neck pain: A randomized controlled trial. J Pain. 2025 Apr;29:105336. doi: 10.1016/j.jpain.2025.105336. Epub 2025 Feb 15.
PubMed 39956442Chaikla R, Sremakaew M, Kothan S, Saekho S, Wantanajittikul K, Uthaikhup S. Effects of manual therapy combined with therapeutic exercise versus routine physical therapy on brain biomarkers in patients with chronic non-specific neck pain in Thailand: a study protocol for a single-blinded randomised controlled trial. BMJ Open. 2023 Apr 24;13(4):e072624. doi: 10.1136/bmjopen-2023-072624.
PubMed 37094892
Study at a glance
From the registry record, last updated by the sponsor on 7 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Manual Therapy Combined With Therapeutic Exercise on Brain Biomarkers in Patients With Chronic Nonspecific Neck Pain: Study Protocol for a Randomized Controlled Trial.
- ClinicalTrials.gov ID
- NCT05568394
- Acronym / sponsor ID
- FF-65 2301484
- Conditions
- Neck Pain
- Keywords
- Neck pain, Manual therapy, Exercise, Magnetic resonance imaging, Magnetic resonance spectroscopy
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 52 participants (actual)
- Lead sponsor
- Chiang Mai UniversityUniversity, hospital or other
- Study start
- 15 Nov 2022 (actual)
- Primary completion
- 28 Nov 2023 (actual)
- Study completion
- 5 Feb 2024 (actual)
- First posted
- 5 Oct 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.
Structural brain alterations in pain-related areas have been demonstrated in patients with nonspecific neck pain. While manual therapy combined with therapeutic exercise is an effective management for neck pain, its underlying mechanisms are poorly understood. The primary objective of this trial is to investigate the effects of manual therapy combined with therapeutic exercise on brain imaging biomarkers in patients with chronic nonspecific neck pain. The secondary objectives are to assess neurochemical biomarkers, clinical features of neck pain, cervical range of motion and cervical muscle strength.
Detailed description
This study is a single-blinded, randomized controlled trial. Forty-eight participants with chronic nonspecific neck pain will be recruited into the study. Participants will be randomly allocated to either an intervention or control group (1:1 ratio). Participants in the intervention group will receive manual therapy combined with therapeutic exercise for 10 weeks (2 visits per week). The control group will receive routine physical therapy. Primary outcomes are brain imaging biomarkers (cortical gray matter: volume, thickness and area, and white matter: fractional anisotropy and mean diffusivity) in pain-related areas. Secondary outcomes are neurochemical biomarkers (N-acetylaspartate, NAA; creatine, Cr; glutamic acid/glutamine, Glu/Gln; myoinositol, mI; and choline, cho), clinical features (neck pain intensity, duration, neck disability and psychological symptoms), cervical range of motion and cervical muscle strength.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- A single-blinded design
| Arm | Type | Receives |
|---|---|---|
| Intervention group | Experimental | Other: Manual therapy combinded with therapeutic exerciseManual therapy and therapeutic exercise |
| Control group | Experimental | Other: Routine physical therapyRoutine physical therapy |
Who may qualify
- Ages
- 18 to 59 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- a history of nonspecific neck pain for ≥ 3 months
- an average pain intensity over the past week ≥ 35 mm. on a visual analogue scale (VAS)
Key exclusion criteria (7 listed)
- a history of head and neck injury or surgery
- known or suspected vestibular pathology or dizziness caused by underlying pathology in the ear, brain and sensory nerve pathways (e.g. benign paroxysmal positional vertigo) and/or vascular disorders
- any neurological or musculoskeletal condition that could affect the outcomes (e.g., scoliosis, torticollis, myofascial pain syndrome, fibromyalgia and rheumatoid arthritis)
- metabolic conditions (e.g., diabetes, obesity (BMI > 30 kg/m2) and hypertension)
- psychological symptoms (e.g., anxiety, depression and schizophrenia)
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 |
|---|---|---|
| Manual therapy combinded with therapeutic exerciseThe treatment includes cervical mobilization and specific therapeutic exercises: craniocervical and cervical flexors and extensors, axioscapular muscles, and postural correction (30-40 minutes). The participants will attend 20 individual treatment sessions (2 visits per week for 10 weeks). | Other | Intervention group |
| Routine physical therapyThe treatment includes routine physical therapy (e.g., modalities, range of motion and/or gentle stretching exercise) (30-40 minutes). The participants will attend 20 individual treatment sessions (2 visits per week for 10 weeks). | Other | Control group |
Primary outcome
Cortical gray matter: volume and thickness
Time frame: At baseline and post-intervention
Cortical gray matter (volume and thickness) will be measured in pain-related areas (thalamus, prefrontal cortex (PFC), primary somatosensory cortex (S1), primary motor cortex (M1), insula, cingulate cortex, precuneus, temporal lobe and periaqueductal gray matter) using a Magnetic resonance imaging (MRI) machine
7 secondary outcomes
Neurochemical biomarkers: N-acetylaspartate (NAA), creatine (Cr), glutamic acid/glutamine (Glu/Gln), myoinositol (mI), and choline (cho)
Time frame: At baseline and post-intervention
Neck pain intensity
Time frame: At baseline and post-intervention
Neck pain and disability
Time frame: At baseline and post-intervention
Anxiety and depression
Time frame: At baseline and post-intervention
Cervical range of motion
Time frame: At baseline and post-intervention
Cervical muscle strength
Time frame: At baseline and post-intervention
White matter integrity: fractional anisotropy (FA) and mean diffusivity (MD)
Time frame: At baseline and post-intervention
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 7 Feb 2024.
- BackgroundJull G, Falla D, Treleaven J, O'Leary S. Management of neck pain disorders: a research informed approach. Edinburgh: Elseiver Limited; 2019.
- Background: PubMed 25306220Johnston V, O'Leary S, Comans T, Straker L, Melloh M, Khan A, Sjogaard G. A workplace exercise versus health promotion intervention to prevent and reduce the economic and personal burden of non-specific neck pain in office personnel: protocol of a cluster-randomised controlled trial. J Physiother. 2014 Dec;60(4):233; discussion 233. doi: 10.1016/j.jphys.2014.08.007. Epub 2014 Oct 11.
- Background: PubMed 29433500Sremakaew M, Jull G, Treleaven J, Barbero M, Falla D, Uthaikhup S. Effects of local treatment with and without sensorimotor and balance exercise in individuals with neck pain: protocol for a randomized controlled trial. BMC Musculoskelet Disord. 2018 Feb 13;19(1):48. doi: 10.1186/s12891-018-1964-3.
- BackgroundMaitland GD, Hengeveld E, Banks K, Anglaise K. Vertebral manipulation. 7th ed. Oxford: Butterworth-Heinemann: Elsevier; 2005.
- Background: PubMed 35210851de Zoete RMJ, Stanwell P, Weber KA, Snodgrass SJ. Differences in Structural Brain Characteristics Between Individuals with Chronic Nonspecific Neck Pain and Asymptomatic Controls: A Case-Control Study. J Pain Res. 2022 Feb 18;15:521-531. doi: 10.2147/JPR.S345365. eCollection 2022.
- Background: PubMed 29327392Coppieters I, De Pauw R, Caeyenberghs K, Lenoir D, DeBlaere K, Genbrugge E, Meeus M, Cagnie B. Differences in white matter structure and cortical thickness between patients with traumatic and idiopathic chronic neck pain: Associations with cognition and pain modulation? Hum Brain Mapp. 2018 Apr;39(4):1721-1742. doi: 10.1002/hbm.23947. Epub 2018 Jan 11.
- Background: PubMed 31773541Didehdar D, Kamali F, Yoosefinejad AK, Lotfi M. The effect of spinal manipulation on brain neurometabolites in chronic nonspecific low back pain patients: a randomized clinical trial. Ir J Med Sci. 2020 May;189(2):543-550. doi: 10.1007/s11845-019-02140-2. Epub 2019 Nov 26.
- Derived from this study: PubMed 39956442Chaikla R, Sremakaew M, Saekho S, Kothan S, Uthaikhup S. Effects of manual therapy combined with therapeutic exercise on brain structure in patients with chronic nonspecific neck pain: A randomized controlled trial. J Pain. 2025 Apr;29:105336. doi: 10.1016/j.jpain.2025.105336. Epub 2025 Feb 15.
- Derived from this study: PubMed 37094892Chaikla R, Sremakaew M, Kothan S, Saekho S, Wantanajittikul K, Uthaikhup S. Effects of manual therapy combined with therapeutic exercise versus routine physical therapy on brain biomarkers in patients with chronic non-specific neck pain in Thailand: a study protocol for a single-blinded randomised controlled trial. BMJ Open. 2023 Apr 24;13(4):e072624. doi: 10.1136/bmjopen-2023-072624.
- 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.
Sureeporn Uthaikhup, PhD. principal investigator
Department of physical therapy, Chiang Mai university
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Manual therapy combinded with therapeutic exercise and Routine physical therapy in people with Neck Pain, run by Chiang Mai University at 1 site in Thailand.
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 2 inclusion and 7 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 7 Feb 2024. 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 Thailand. 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?
Cortical gray matter: volume and thickness (time frame: At baseline and post-intervention). 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 NCT05568394, which also lists 9 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 7 Feb 2024.