Clinical Trial Details
— Status: Terminated
Administrative data
| NCT number |
NCT04067544 |
| Other study ID # |
107709 |
| Secondary ID |
|
| Status |
Terminated |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
November 5, 2019 |
| Est. completion date |
August 12, 2020 |
Study information
| Verified date |
August 2020 |
| Source |
University of Utah |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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.
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.
