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Acupuncture Treatment of Chemotherapy-Induced Peripheral Neuropathy in Women

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ClinicalTrials.gov Identifier: NCT04067544
Recruitment Status : Terminated (Unforeseen complications due to COVID-19 and funding)
First Posted : August 26, 2019
Last Update Posted : August 17, 2020
Sponsor:
Information provided by (Responsible Party):
Lisa J Taylor-Swanson, University of Utah

Tracking Information
First Submitted Date  ICMJE August 21, 2019
First Posted Date  ICMJE August 26, 2019
Last Update Posted Date August 17, 2020
Actual Study Start Date  ICMJE November 5, 2019
Actual Primary Completion Date August 12, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 21, 2019)
  • Mean monthly enrollment [ Time Frame: 18 Months ]
    Average of 2 eligible women per month to participate in the trial
  • Retention Rate [ Time Frame: 2 Months ]
    70% or more participants comply with AT attendance defined as 8 or more of 10 AT sessions and complete both fMRI scans
  • Number of Serious Adverse Events [ Time Frame: 2 Months ]
    Zero serious adverse events directly related to AT sessions
  • Questionnaire Completion Rate [ Time Frame: 4 Months ]
    70% or more enrolled participants comply with data collection
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Acupuncture Treatment of Chemotherapy-Induced Peripheral Neuropathy in Women
Official Title  ICMJE Acupuncture Treatment of Chemotherapy-Induced Peripheral Neuropathy in Women With Breast or Gynecologic Cancers: Mechanisms of Action and Feasibility
Brief Summary This pilot study aims to evaluate the feasibility to conduct a study of acupuncture treatment (AT) for Chemotherapy-Induced Peripheral Neuropathy (CIPN) at Huntsman Cancer Institute and to investigate changes in physiological biomarkers when using acupuncture to treat CIPN.
Detailed Description

Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common and disabling complications of cancer chemotherapy. CIPN is a major cause of morbidity and reduced quality of life among cancer survivors due to pain, gait instability, and fall related injury. Up to 60% of patients receiving potentially neurotoxic chemotherapeutics develop CIPN, 40% of whom have persistent neuropathy after termination of chemotherapy. CIPN commonly necessitates dose reduction or cessation of therapy, potentially limiting treatment efficacy and likely impacting patient outcomes.First-line treatments include anticonvulsants, tricyclic antidepressants, selective serotonin and norepinephrine reuptake inhibitors (SSNRIs) and topical lidocaine. Second-line treatments include opioids. Given the risk of abuse, overdose and addiction, treatments besides opioids are advised and warrant investigation. A multimodal approach may be most effective, with acupuncture being a safe option reporting low rates of adverse events. Acupuncture treatment (AT) is a well-tolerated and safe treatment option frequently used for symptoms associated with cancer therapies such as nausea, vomiting, xerostomia and fatigue. Several case series and small uncontrolled trials of AT for CIPN suggest potential efficacy, although well-designed and powered clinical trials are lacking and mechanisms underlying AT's potential efficacy are unknown.

Although drug-induced damage to the peripheral nervous system is well recognized in CIPN, the central nervous system (CNS) also shows concomitant involvement. Much of our current understanding of the pathophysiology of central pain processing in chronic painful conditions such as diabetic neuropathy, trigeminal neuralgia, post-herpetic neuralgia and chronic low back pain has utilized functional magnetic resonance imaging (fMRI). Previous pain-related functional studies identified alterations in brain activation in multiple cortical and subcortical regions including the frontal lobe, insular cortex, somatosensory cortex, thalamus, periaqueductal grey and precuneus.

While fMRI has not yet been used to evaluate mechanisms of action of AT in the context of CIPN, an increasing number of studies have applied fMRI to investigate AT over a wide range of pain disorders. Stimulation of acupuncture points is associated with overlapping activity in cortical and subcortical brain regions, including the insula, thalamus, anterior cingulate cortex, primary and secondary somatosensory cortices, and deactivation in limbic-paralimbic-neocortical network. Acupuncture can modulate activity within specific brain areas, many of which are known to be important to CIPN pain processing. The investigators hypothesize that regions involved in pain perception will show decreased connectivity between the insula, amygdala and somatosensory cortex with successful pain treatment, with decreased task-related activation of the brain's salience network (anterior cingulate and frontal insula) during mental pain imagery.

Additionally, neurological evidence indicates that some of the brain regions activated during pain perception are also activated when engaging in interoceptive awareness. Acupuncture has been shown to alter pain processing regions but has not been evaluated regarding changes in mind-body awareness. The possible role of enhanced mind-body awareness as a mechanism of action of acupuncture has not yet been tested. This pilot study will provide a preliminary fMRI and questionnaire data for this topic. Clinical trials of interventions such as mindfulness-based cognitive therapy demonstrate increased interoceptive awareness and decreased depression. It seems plausible that AT may provide an opportunity for participants to increase their mind-body awareness while they lie on the treatment table and relax, as well as via neurologic changes in the insula, amygdala, and somatosensory cortex. These regions are known to affect pain processing as well as interoceptive (or mind-body) awareness.

This pilot feasibility study aims to determine if conducting a trial of AT for CIPN is feasible at HCI. The investigators aim to enroll and retain twenty participants who will undergo fMRI during the baseline visit, receive 10 sessions of AT, and undergo fMRI after completion of AT. The investigators will examine fMRI for potential neurologic mechanisms of action of AT in CIPN management. The ultimate objective of this pilot project is to lay the foundation for a future randomized controlled clinical trial of AT for CIPN. Specifically, the investigators will be able to demonstrate that the investigators have the team and location in place to conduct a successful trial.

The participant will receive 10 acupuncture treatments over the course of 8 weeks with a baseline fMRI done prior to receiving acupuncture treatments and a final fMRI done after the completion of acupuncture treatments. Participant will receive questionnaires before fMRI, acupuncture treatments following final fMRI and at a 3 month follow up time point. (See below for more detail.)

1.1 Primary Objectives and Endpoints

To evaluate the feasibility to conduct a trial of AT for CIPN + standard of care therapy. Primary feasibility objectives will be evaluated in terms of recruitment (enrollment of 20 women, average of 2 eligible women per month to participate in the trial, identification of appropriate recruitment strategies, the appropriateness of eligibility criteria), retention (70% or more participants comply with 8 or more AT sessions and complete both fMRI scans), safety (zero serious adverse events directly related to AT) and questionnaire completion (70% or more enrolled participants comply with all data collection).

1.1.1 Primary outcome measures: Mean enrollment, completion rate of AT, fMRI, rate of serious adverse events, rate of questionnaire completion.

1.2 Secondary Objectives and Endpoints To evaluate the impact of AT on the reported experience of CIPN. 1.2.1 To evaluate central pain processing and cortical connectivity in patients with CIPN treated by acupuncture by analyzing fMRI of all participants.

1.2.2 To evaluate if there is any change in patient-reported measures from before AT to after study completion.

This study will enroll female patients who have completed treatment with paclitaxel or docetaxel at least three months prior. Paclitaxel and docetaxel are neurotoxic chemotherapies known to cause CIPN. Patients must have experienced at least one month of altered sensation and/or pain with a score of greater than or equal to 20 for CIPN on the sensory subscale of the CIPN-20. The investigators will commence recruitment 3 months after patients have completed their last paclitaxel or docetaxel dose. Patients will be recruited from the Huntsman Cancer Center Oncology Clinics in collaboration with their oncologists.

For this study, enrollment will be limited to patients with breast, ovarian, cervical, endometrial, or uterine cancer with CIPN and completed paclitaxel or docetaxel treatments.

Visits:

Screening Visit:

Potentially eligible subjects will be scheduled for a screening visit. After informed consent is obtained, the SC will review and confirm inclusion/exclusion criteria. The SC will take a brief medical and neurological history and administer the CIPN-20 questionnaire. If all inclusion and exclusion criteria are fulfilled, the subject will proceed to baseline visit. This visit may occur on the same day as screening, but must occur within 2 weeks of study screening visit.

Baseline Visit:

Patients diagnosed with breast, ovarian, cervical, endometrial, or uterine cancer who were treated with paclitaxel or docetaxel chemotherapy associated with CIPN will undergo a number of questionnaires/exam scales designed to assess neuropathic symptoms and the effect of neuropathy on quality of life. The patient will then be enrolled in the study and scheduled in the Wellness Center for acupuncture therapy (AT). All participants will be scheduled for fMRI , which must occur within nine days after baseline.

Participants will undergo study interview and fMRI within 9 days after baseline following enrollment.

Demographic data and clinical data including current medications and medical history and fall rates will be gathered during the baseline visit. Questionnaires (BPI, CIPN-20, CIPN-R-ODS, MAIA-2) will be completed in person or emailed to patients via REDCap at baseline. Reminder calls and AT appointments will be scheduled by HCI Wellness and Integrative Health Center personnel in conjunction with a SC. The SC will aid participants in scheduling fMRI appointments online. AT treatments will occur within 7 days/4 business days in general.

Follow up Visits:

Participants will receive 10 sessions of AT: twice per week for 2 weeks, thereafter once per week for six weeks, with a total of 10 treatments during a two-month course. Each session will last 45-60 minutes, with acupuncture needles retained 30-40 minutes. A minimum of 8 treatments must be received by each participant with no more than 9 days' gap between weekly treatments permitted (sessions 5-10). Concurrent medications are allowed as prescribed and will be tracked in the study and analyzed as potential confounders.

Final Visit:

Participants will undergo examination within one week of AT completion. This will include the fMRI scan and questionnaires. Compensation for participation will be offered following the completion of questionnaires.

Measures:

Questionnaires will be completed in person or emailed to patients via REDCap at baseline and study conclusion, as well as at a 3-month follow-up. Primary Endpoints: Mean enrollment, percentage completion rate of all study procedures, frequency count of serious adverse events, and percentage of enrolled participants completing questionnaires will be calculated. Data will be collected via REDCap and analyzed with SPSS.

Additional measures to be collected: CIPN-20: This measure includes questions about tingling, numbness, painful numbness, cramps, balance, temperature intolerance, grasping items, ankle flexion weakness and leg weakness. CIPN-R-ODS (a validated measure of quality of life specific to CIPN), will be used to assess impact on function, BPI to assess pain and Multidimensional Assessment of Interoceptive Awareness (MAIA-2) to assess mind-body awareness. The investigators will also collect demographic information including age, marital status, race and ethnicity, current medications and medical history.

Acupuncture therapy (AT): AT will be delivered onsite at HCI in the Linda B. and Robert B. Wiggins Wellness & Integrative Health Center. AT will be delivered twice per week for two weeks and then weekly for six weeks by Annie Budhathoki, DAOM, a Licensed Acupuncturist who has over five years' clinical experience treating persons with cancer, or another Licensed Acupuncturist in the Wellness & Integrative Health Center. Each session will last 45-60 minutes, with acupuncture needles retained 30-40 minutes. A minimum of 8 treatments must be received by each participant with no more than 9 days' gap between weekly treatments permitted (sessions 5-10). .

Functional MRI (fMRI) to be conducted within 9 days after baseline and within 1 week of final AT session. fMRI scans will be conducted at Imaging and Neuroscience Center (INC) in Research Park. Imaging will consist of structural brain imaging (MP2RAGE), task fMRI, and resting-state fMRI connectivity. Task fMRI will consist of a mental imagery task with a 20-second block design wherein patients will alternate between concentration on a part of their body where they experience pain and a part of their body where they do not experience pain, prompted by visual cues. The investigators will provide gift cards for $25 after the completion of the second fMRI and questionnaires associated with this visit.

Clinical evaluations: Demographic data, clinical data including current medications and medical history and fall rates will be gathered.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Condition  ICMJE
  • Chemotherapy-induced Peripheral Neuropathy
  • Breast Cancer Female
  • Gynecologic Cancer
Intervention  ICMJE Device: Acupuncture

The manualized acupuncture treatment (AT) intervention will be designed by Dr. Budhathoki and Dr. Taylor-Swanson and administered by Dr. Budhathoki and members of Huntsman acupuncture team. Ten sessions of AT will be delivered: twice per week for 2 weeks, thereafter once per week for six weeks, with a total of 9 treatments during a two-month course. Each session will last 45-60 minutes, with acupuncture needles retained 30-40 minutes. A minimum of 8 treatments must be received by each participant with no more than 9 days' gap between treatments permitted. Concurrent medications are allowed as prescribed and will be tracked in the study and analyzed as potential confounders.

Participants in the study will undergo study interview and fMRI at the following two time points: within 9 days after baseline following enrollment and within one week of acupuncture treatment completion.

Study Arms  ICMJE Acupuncture Treatment
All patients receive 10 acupuncture treatments over the course of 8 weeks.
Intervention: Device: Acupuncture
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: August 12, 2020)
3
Original Estimated Enrollment  ICMJE
 (submitted: August 21, 2019)
20
Actual Study Completion Date  ICMJE August 12, 2020
Actual Primary Completion Date August 12, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

Female age 18 or older.

  • Histologically proven breast, uterine, cervical or ovarian cancer of any stage.
  • Received either (1) a Paclitaxel treatment dose of at least 480 mg/m2 paclitaxel as a single or combination agent or (2) a Docetaxel treatment dose of at least 150 mg/m2 docetaxel as a single or combination agent. Treatment must be completed at least 3 months prior to enrollment.
  • Eligible patients report at least 1 month of altered sensation and/or pain in the feet (with or without presence in one or both hands) with a score of greater than or equal to 20 for CIPN on the sensory subscale of the CIPN-20 (scale 0-100).
  • Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines.
  • ECOG status of 0 (asymptomatic), 1 (symptomatic but completely ambulatory) or 2 (symptomatic, <50% in bed during the day).

Exclusion Criteria:

  • Preexisting neuropathy due to other identified etiologies includes diabetes, vitamin B12 deficiency, or alcoholism.
  • Having received more than 6 acupuncture treatments for any condition in the last six months.
  • Patients with claustrophobia, pacemakers, non-MRI compatible breast expanders or port-a-caths, neurostimulator devices, current pregnancy, exposure to shrapnel, left-handedness, or otherwise unsafe for MRI scanning.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04067544
Other Study ID Numbers  ICMJE 107709
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Lisa J Taylor-Swanson, University of Utah
Study Sponsor  ICMJE University of Utah
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Lisa J Taylor-Swanson, PhD LAc Associate Professor of College of Nursing, Licensed Acupunturist
PRS Account University of Utah
Verification Date August 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP