Clinical trial NCT05568394: Effects of Manual Therapy Combined With Therapeutic Exercise on Brain Biomarkers in Neck Pain
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Neck Pain
Keywords: Neck pain
Manual therapy
Exercise
Magnetic resonance imaging
Magnetic resonance spectroscopy
Lead sponsor: Chiang Mai University
Sponsor class: OTHER
First posted: 2022-10-05
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Maximum age (years): 59
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A single-blinded design
Primary purpose: TREATMENT

Brief 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. 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.

Eligibility criteria: Inclusion Criteria:

* 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)

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Cortical gray matter: volume and thickness
timeFrame: At baseline and post-intervention
Secondary outcomes:
measure: Neurochemical biomarkers: N-acetylaspartate (NAA), creatine (Cr), glutamic acid/glutamine (Glu/Gln), myoinositol (mI), and choline (cho)
timeFrame: At baseline and post-intervention
measure: Neck pain intensity
timeFrame: At baseline and post-intervention
measure: Neck pain and disability
timeFrame: At baseline and post-intervention
measure: Anxiety and depression
timeFrame: At baseline and post-intervention
measure: Cervical range of motion
timeFrame: At baseline and post-intervention
measure: Cervical muscle strength
timeFrame: At baseline and post-intervention
measure: White matter integrity: fractional anisotropy (FA) and mean diffusivity (MD)
timeFrame: At baseline and post-intervention
Other outcomes:
Locations:
city: Chiang Mai
country: Thailand
facility: Department of Physical Therapy, Faculty of Associated Medical Sciences
Study officials:
affiliation: Department of physical therapy, Chiang Mai university
name: Sureeporn Uthaikhup, PhD.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Jull G, Falla D, Treleaven J, O'Leary S. Management of neck pain disorders: a research informed approach. Edinburgh: Elseiver Limited; 2019.
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citation: Sremakaew 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.
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citation: 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.
citation: Coppieters 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.
citation: Didehdar 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.