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Cytokine and Growth Factor Changes and Correlation With Clinical Outcomes Following Acupuncture for TMD

Primary Purpose

Temporomandibular Joint Disorders

Status
Withdrawn
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Acupuncture
Sham Acupuncture
Sponsored by
University of North Carolina, Chapel Hill
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Temporomandibular Joint Disorders

Eligibility Criteria

18 Years - 64 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Signed, informed consent; females and males aged 18-64; planning on living in the area for the next 2 months; fluent in written and spoken English;

Myofascial pain with referral diagnosed according to TMD diagnostic criteria (Schiffman et al. 2014):

pain in the temporalis and masseter muscles report of familiar pain with palpation of the two muscles report of pain at a site beyond the boundary of the muscle being palpated.

Exclusion Criteria:

Traumatic facial injury or surgery on the face or jaw; currently receiving orthodontic treatment;

Systemic inflammatory disorders such as lupus, kidney failure or renal dialysis, heart disease or heart failure, chronic respiratory disease, hypertension, un- controlled diabetes, epilepsy or seizures

Hyperthyroidism; chemotherapy or radiation therapy; trigeminal neuralgia; cluster headache;

Drug or alcohol abuse; active or uncontrolled psychiatric disorders or recent (within 6 months) psychiatric hospitalization; pending pension or worker's claim/litigation; previous experience with acupuncture for TMD

Current use of NSAIDS and/or steroidal medications.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Active Comparator

    Sham Comparator

    Arm Label

    Acupuncture

    Sham Acupuncture

    Arm Description

    Acupuncture treatment for TMD

    Acupuncture treatment for TMD using the non-penetrating Park Sham Acupuncture Device

    Outcomes

    Primary Outcome Measures

    Change in cytokine IL-8 levels in circulating blood and saliva after 4 weeks of real acupuncture compared with 4 weeks of sham acupuncture.

    Secondary Outcome Measures

    Change in patient-reported symptoms on the Measure Yourself Medical Outcome Profile (MYMOP; a 1-page paper questionnaire) after 4 weeks of real acupuncture compared with 4 weeks of sham acupuncture.
    Change in patient-reported pain intensity on the Pain Scale (a 1-page paper questionnaire) after 4 weeks of real acupuncture compared with 4 weeks of sham acupuncture.
    Change in cytokine MCP-1 levels in circulating blood and saliva after 4 weeks of real acupuncture compared with 4 weeks of sham acupuncture.
    Change in cytokine IL-1ra levels in circulating blood and saliva after 4 weeks of real acupuncture compared with 4 weeks of sham acupuncture.
    Change in cytokine IL-2 levels in circulating blood and saliva prior to and after real acupuncture compared with sham acupuncture at study Week 1.
    Change in cytokine IL-4 levels in circulating blood and saliva prior to and after real acupuncture compared with sham acupuncture at study Week 1.
    Change in cytokine IL-6 levels in circulating blood and saliva prior to and after real acupuncture compared with sham acupuncture at study Week 1.
    Change in cytokine IL-10 levels in circulating blood and saliva prior to and after real acupuncture compared with sham acupuncture at study Week 1.
    Change in cytokine IL-2 levels in circulating blood and saliva prior to and after real acupuncture compared with sham acupuncture at study Week 4.
    Change in cytokine IL-4 levels in circulating blood and saliva prior to and after real acupuncture compared with sham acupuncture at study Week 4.
    Change in cytokine IL-6 levels in circulating blood and saliva prior to and after real acupuncture compared with sham acupuncture at study Week 4.
    Change in cytokine IL-10 levels in circulating blood and saliva prior to and after real acupuncture compared with sham acupuncture at study Week 4.
    Change in nerve growth factor (NGF) levels in circulating blood prior to and after real acupuncture compared with sham acupuncture at study Week 1.
    Change in vascular endothelial growth factor (VEGF) levels in circulating blood prior to and after real acupuncture compared with sham acupuncture at study Week 1.
    Change in platelet-derived growth factor (PDGF) levels in circulating blood prior to and after real acupuncture compared with sham acupuncture at study Week 1.
    Change in basic fibroblast growth factor (bFGF) levels in circulating blood prior to and after real acupuncture compared with sham acupuncture at study Week 1.
    Change in tumor necrosis factor alpha (TNFa) levels in circulating blood prior to and after real acupuncture compared with sham acupuncture at study Week 1.
    Change in nerve growth factor (NGF) levels in circulating blood prior to and after real acupuncture compared with sham acupuncture at study Week 4.
    Change in vascular endothelial growth factor (VEGF) levels in circulating blood prior to and after real acupuncture compared with sham acupuncture at study Week 4.
    Change in platelet-derived growth factor (PDGF) levels in circulating blood prior to and after real acupuncture compared with sham acupuncture at study Week 4.
    Change in basic fibroblast growth factor (bFGF) levels in circulating blood prior to and after real acupuncture compared with sham acupuncture at study Week 4.
    Change in tumor necrosis factor alpha (TNFa) levels in circulating blood prior to and after real acupuncture compared with sham acupuncture at study Week 4.

    Full Information

    First Posted
    December 19, 2014
    Last Updated
    February 22, 2016
    Sponsor
    University of North Carolina, Chapel Hill
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    1. Study Identification

    Unique Protocol Identification Number
    NCT02324712
    Brief Title
    Cytokine and Growth Factor Changes and Correlation With Clinical Outcomes Following Acupuncture for TMD
    Official Title
    Cytokine and Growth Factor Changes and Correlation With Clinical Outcomes Following Acupuncture for TMD
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    February 2016
    Overall Recruitment Status
    Withdrawn
    Why Stopped
    PI relocated to another institution; study may be resubmitted at a later date.
    Study Start Date
    undefined (undefined)
    Primary Completion Date
    February 2016 (Actual)
    Study Completion Date
    undefined (undefined)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    University of North Carolina, Chapel Hill

    4. Oversight

    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    Purpose: 1) To investigate differences in pro-inflammatory and anti-inflammatory cytokines and growth factors in the circulating blood (and cytokine levels only in saliva) of patients with chronic temporomandibular disorder (TMD) before and after acupuncture; 2) To determine differences in cytokine profiles between real and sham acupuncture in circulating blood of patients with chronic TMD; and 3) To explore correlations between these changes and clinical outcomes. Participants: Patients with chronic TMD pain recruited through the University of North Carolina-Chapel Hill (UNC-CH) Orofacial Pain Clinic. Procedures (methods): Participants will complete a self-administered questionnaire assessing TMD-related comorbidity. During the initial visit, study examiners will record clinical characteristics of muscles and joints of the head, neck and body according to newly recommended diagnostic criteria (DC) for TMD. Clinical outcomes include a pain index (computed from numeric rating scales) of masseter, temporalis and the supplemental painful muscles, and patient-reported symptoms (using the Measure Yourself Medical Outcome Profile; MYMOP) and pain intensity (using the Pain Scale). Blood (5 cc) will be taken before and after acupuncture treatments. Participants will self-collect pre-treatment and post-treatment saliva samples. Patients will receive 4 acupuncture treatments, once per week for 4 weeks. The primary outcome measure is change in IL-8 levels in circulating blood and saliva after 4 weeks of real acupuncture compared with sham acupuncture. Secondary outcome measures include comparing changes in levels of nerve growth factor (NGF), tumor necrosis factor-alpha (TNFα),vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF), and IL-1α, IL-2, IL-4, IL-6 and IL-10, before and after real acupuncture at Week 1 compared with sham acupuncture and before and after real acupuncture at Week 4 compared with sham acupuncture. The exploratory outcome measure is correlation between changes in cytokine levels and clinical variables after 4 weeks of real acupuncture compared with 4 weeks of sham acupuncture.
    Detailed Description
    Temporomandibular disorder (TMD) is known to be the second most frequent musculoskeletal pain condition following low back pain. According to the NIDCR, TMD affects 5%-12% of the population at an annual cost estimated at 4 billion dollars in the US. Recent studies that have investigated acupuncture as a treatment for musculoskeletal pain have reported various results. Several meta-analyses and systematic reviews of randomized controlled trials suggest that acupuncture treatment improves TMD-related pain. Its mechanism of action in improving TMD pain, however, is largely unclear. Elevated levels of pro-inflammatory cytokines, e.g., MCP-1 and IL-8 have been found in circulating blood of patients with TMD. Upregulated pro-inflammatory cytokine levels have been correlated with greater sensitivity to pain evoking stimuli. Abnormalities in levels of pro-inflammatory cytokines are often accompanied by alterations in levels of anti-inflammatory cytokines, e.g., IL-1ra, which are associated with reductions in pain and inflammation. The effects of acupuncture on pro- and anti-inflammatory cytokines, growth factors, and clinical pain and function have not been reported in a prospective cohort of TMD patients at multiple time points in the clinical setting. The proposed mechanistic study seeks to ascertain if acupuncture compared to sham acupuncture produces measurable changes in circulating pro- and anti-inflammatory cytokines and growth factors in a manner that is associated with patient self-reports of pain and function over a 4-week treatment period. Cytokine and growth factor levels will be measured in blood and saliva; saliva will be used to measure cytokine levels only.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Temporomandibular Joint Disorders

    7. Study Design

    Primary Purpose
    Basic Science
    Study Phase
    Not Applicable
    Interventional Study Model
    Parallel Assignment
    Masking
    Participant
    Allocation
    Randomized
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Acupuncture
    Arm Type
    Active Comparator
    Arm Description
    Acupuncture treatment for TMD
    Arm Title
    Sham Acupuncture
    Arm Type
    Sham Comparator
    Arm Description
    Acupuncture treatment for TMD using the non-penetrating Park Sham Acupuncture Device
    Intervention Type
    Device
    Intervention Name(s)
    Acupuncture
    Intervention Description
    Acupuncture using standard stainless steel acupuncture needles inserted into intramuscular tissue for 20 minutes
    Intervention Type
    Device
    Intervention Name(s)
    Sham Acupuncture
    Intervention Description
    Acupuncture using non-penetrating Park Sham Needles for 20 minutes
    Primary Outcome Measure Information:
    Title
    Change in cytokine IL-8 levels in circulating blood and saliva after 4 weeks of real acupuncture compared with 4 weeks of sham acupuncture.
    Time Frame
    Baseline, 4 weeks
    Secondary Outcome Measure Information:
    Title
    Change in patient-reported symptoms on the Measure Yourself Medical Outcome Profile (MYMOP; a 1-page paper questionnaire) after 4 weeks of real acupuncture compared with 4 weeks of sham acupuncture.
    Time Frame
    Baseline, 4 weeks
    Title
    Change in patient-reported pain intensity on the Pain Scale (a 1-page paper questionnaire) after 4 weeks of real acupuncture compared with 4 weeks of sham acupuncture.
    Time Frame
    Baseline, 4 weeks
    Title
    Change in cytokine MCP-1 levels in circulating blood and saliva after 4 weeks of real acupuncture compared with 4 weeks of sham acupuncture.
    Time Frame
    Baseline, 4 weeks
    Title
    Change in cytokine IL-1ra levels in circulating blood and saliva after 4 weeks of real acupuncture compared with 4 weeks of sham acupuncture.
    Time Frame
    Baseline, 4 weeks
    Title
    Change in cytokine IL-2 levels in circulating blood and saliva prior to and after real acupuncture compared with sham acupuncture at study Week 1.
    Time Frame
    Week 1
    Title
    Change in cytokine IL-4 levels in circulating blood and saliva prior to and after real acupuncture compared with sham acupuncture at study Week 1.
    Time Frame
    Week 1
    Title
    Change in cytokine IL-6 levels in circulating blood and saliva prior to and after real acupuncture compared with sham acupuncture at study Week 1.
    Time Frame
    Week 1
    Title
    Change in cytokine IL-10 levels in circulating blood and saliva prior to and after real acupuncture compared with sham acupuncture at study Week 1.
    Time Frame
    Week 1
    Title
    Change in cytokine IL-2 levels in circulating blood and saliva prior to and after real acupuncture compared with sham acupuncture at study Week 4.
    Time Frame
    Week 4
    Title
    Change in cytokine IL-4 levels in circulating blood and saliva prior to and after real acupuncture compared with sham acupuncture at study Week 4.
    Time Frame
    Week 4
    Title
    Change in cytokine IL-6 levels in circulating blood and saliva prior to and after real acupuncture compared with sham acupuncture at study Week 4.
    Time Frame
    Week 4
    Title
    Change in cytokine IL-10 levels in circulating blood and saliva prior to and after real acupuncture compared with sham acupuncture at study Week 4.
    Time Frame
    Week 4
    Title
    Change in nerve growth factor (NGF) levels in circulating blood prior to and after real acupuncture compared with sham acupuncture at study Week 1.
    Time Frame
    Week 1
    Title
    Change in vascular endothelial growth factor (VEGF) levels in circulating blood prior to and after real acupuncture compared with sham acupuncture at study Week 1.
    Time Frame
    Week 1
    Title
    Change in platelet-derived growth factor (PDGF) levels in circulating blood prior to and after real acupuncture compared with sham acupuncture at study Week 1.
    Time Frame
    Week 1
    Title
    Change in basic fibroblast growth factor (bFGF) levels in circulating blood prior to and after real acupuncture compared with sham acupuncture at study Week 1.
    Time Frame
    Week 1
    Title
    Change in tumor necrosis factor alpha (TNFa) levels in circulating blood prior to and after real acupuncture compared with sham acupuncture at study Week 1.
    Time Frame
    Week 1
    Title
    Change in nerve growth factor (NGF) levels in circulating blood prior to and after real acupuncture compared with sham acupuncture at study Week 4.
    Time Frame
    Week 4
    Title
    Change in vascular endothelial growth factor (VEGF) levels in circulating blood prior to and after real acupuncture compared with sham acupuncture at study Week 4.
    Time Frame
    Week 4
    Title
    Change in platelet-derived growth factor (PDGF) levels in circulating blood prior to and after real acupuncture compared with sham acupuncture at study Week 4.
    Time Frame
    Week 4
    Title
    Change in basic fibroblast growth factor (bFGF) levels in circulating blood prior to and after real acupuncture compared with sham acupuncture at study Week 4.
    Time Frame
    Week 4
    Title
    Change in tumor necrosis factor alpha (TNFa) levels in circulating blood prior to and after real acupuncture compared with sham acupuncture at study Week 4.
    Time Frame
    Week 4

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    64 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Signed, informed consent; females and males aged 18-64; planning on living in the area for the next 2 months; fluent in written and spoken English; Myofascial pain with referral diagnosed according to TMD diagnostic criteria (Schiffman et al. 2014): pain in the temporalis and masseter muscles report of familiar pain with palpation of the two muscles report of pain at a site beyond the boundary of the muscle being palpated. Exclusion Criteria: Traumatic facial injury or surgery on the face or jaw; currently receiving orthodontic treatment; Systemic inflammatory disorders such as lupus, kidney failure or renal dialysis, heart disease or heart failure, chronic respiratory disease, hypertension, un- controlled diabetes, epilepsy or seizures Hyperthyroidism; chemotherapy or radiation therapy; trigeminal neuralgia; cluster headache; Drug or alcohol abuse; active or uncontrolled psychiatric disorders or recent (within 6 months) psychiatric hospitalization; pending pension or worker's claim/litigation; previous experience with acupuncture for TMD Current use of NSAIDS and/or steroidal medications.
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Jongbae (Jay) Park, KMD, PhD
    Organizational Affiliation
    University of North Carolina, Chapel Hill
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    20401353
    Citation
    Cho SH, Whang WW. Acupuncture for temporomandibular disorders: a systematic review. J Orofac Pain. 2010 Spring;24(2):152-62.
    Results Reference
    background
    PubMed Identifier
    20551730
    Citation
    La Touche R, Goddard G, De-la-Hoz JL, Wang K, Paris-Alemany A, Angulo-Diaz-Parreno S, Mesa J, Hernandez M. Acupuncture in the treatment of pain in temporomandibular disorders: a systematic review and meta-analysis of randomized controlled trials. Clin J Pain. 2010 Jul-Aug;26(6):541-50. doi: 10.1097/AJP.0b013e3181e2697e.
    Results Reference
    background
    PubMed Identifier
    22000099
    Citation
    Slade GD, Conrad MS, Diatchenko L, Rashid NU, Zhong S, Smith S, Rhodes J, Medvedev A, Makarov S, Maixner W, Nackley AG. Cytokine biomarkers and chronic pain: association of genes, transcription, and circulating proteins with temporomandibular disorders and widespread palpation tenderness. Pain. 2011 Dec;152(12):2802-2812. doi: 10.1016/j.pain.2011.09.005. Epub 2011 Oct 14.
    Results Reference
    background

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    Cytokine and Growth Factor Changes and Correlation With Clinical Outcomes Following Acupuncture for TMD

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