NCT03687970

Brief Summary

The investigators propose that using the Diode Laser fiber type Selective Stimulator (DLss) in patients with chemotherapy-induced peripheral neuropathy (CIPN) will allow for the assessment of changes in small-fiber pain thresholds, to identify differences between subjects who received chemotherapy and developed painful CIPN, compared to subjects who received similar chemotherapy but did not develop painful CIPN (control group). Additionally, the investigators would like to investigate whether the response to DLss correlates with pain severity in patients with persistent painful neuropathy. The ultimate goal of this study is to develop a non-invasive, bedside quantitative test that is specific for painful CIPN. If the investigators' initial hypothesis is confirmed, the next step would be to design a prospective longitudinal study and assess changes in DLss early after initiation of chemotherapy, to determine whether this approach can help identify early predictive parameters of painful CIPN.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
42

participants targeted

Target at P25-P50 for not_applicable

Timeline
Completed

Started Sep 2018

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

September 17, 2018

Completed
8 days until next milestone

First Submitted

Initial submission to the registry

September 25, 2018

Completed
2 days until next milestone

First Posted

Study publicly available on registry

September 27, 2018

Completed
12 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 17, 2019

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 17, 2019

Completed
1.1 years until next milestone

Results Posted

Study results publicly available

October 22, 2020

Completed
Last Updated

May 19, 2021

Status Verified

April 1, 2021

Enrollment Period

1 year

First QC Date

September 25, 2018

Results QC Date

August 29, 2020

Last Update Submit

April 28, 2021

Conditions

Keywords

CIPNNeuropathic painDLssPeripheral neuropathy

Outcome Measures

Primary Outcomes (1)

  • Aδ:C Fiber Detection Threshold Ratio

    Comparison of the Aδ:C fiber detection threshold ratio (as measured by the DLss) between patients with painful neuropathy and patients who did not develop painful neuropathy following similar cancer chemotherapy

    At the time of the DLss (day 1)

Secondary Outcomes (2)

  • The Aδ:C Pain Threshold Ratio

    At the time of the DLss (day 1)

  • The Severity of Neuropathy on NPSI Scale.

    At the time of the DLss (day 1)

Study Arms (2)

Group A: Painful CIPN Group

EXPERIMENTAL

-Performed at baseline: NPSI, BPI, HADS, Spontaneous pain at baseline on 0-10 Numerical Rating Scale (NRS), QST, CPM, and DLss

Other: Brief Pain InventoryOther: Hospital Anxiety and Depression ScaleOther: Neuropathic Pain Symptom InventoryProcedure: Diode Laser fiber type Selective StimulatorProcedure: Quantitative sensory testingProcedure: Conditioned pain modulation efficiencyOther: Spontaneous pain at baseline on 0-10 Numerical Rating Scale (NRS)

Group B: Control Group

ACTIVE COMPARATOR

-Performed at baseline: NPSI, BPI, HADS, Spontaneous pain at baseline on 0-10 Numerical Rating Scale (NRS), QST, CPM, and DLss

Other: Brief Pain InventoryOther: Hospital Anxiety and Depression ScaleOther: Neuropathic Pain Symptom InventoryProcedure: Diode Laser fiber type Selective StimulatorProcedure: Quantitative sensory testingProcedure: Conditioned pain modulation efficiencyOther: Spontaneous pain at baseline on 0-10 Numerical Rating Scale (NRS)

Interventions

-A self-administered questionnaire used to evaluate the severity of a patient's pain and the impact of this pain on the patient's daily functioning. The patient is asked to rate their worst, least, average, and current pain intensity (4 items which generate the PAIN SEVERITY score), list current treatments and their perceived effectiveness, and rate the degree that pain interferes with general activity, mood, walking ability, normal work, relations with other persons, sleep, and enjoyment of life (7 items which generate the PAIN INTERFERENCE score) on a 10 point scale.

Also known as: BPI
Group A: Painful CIPN GroupGroup B: Control Group

* 14 item scale with even of the items relating to anxiety and seven relating to depression * Each item on the questionnaire is scored from 0-3 and this means that a patient can score between 0 and 21 for either anxiety or depression

Also known as: HADS
Group A: Painful CIPN GroupGroup B: Control Group

-The NPSI questionnaire utilized in this study includes eight parameters (i.e., burning pain, squeezing pain, pressure pain, electric shock pain, stabbing pain, tingling pain, pins and needles pain and allodynia \[pain provoked by light touch\]). Each of the parameters includes recall of the past 24 hours

Also known as: NPSI
Group A: Painful CIPN GroupGroup B: Control Group

-Each patient will have an A and C fiber stimulation. Stimulation will be performed on the dorsum of the foot using stimulation previously published parameters to elicit "burning pain," which is from activation of C-fibers and "pinprick" pain from A-fibers

Also known as: DLss
Group A: Painful CIPN GroupGroup B: Control Group

* Quantitative sensory testing will be performed on the dorsal mid-foot and the ipsilateral shoulder will serve as control area * Cold and warm detection thresholds, cold and heat pain thresholds, mechanical detection thresholds, and wind-up ratio

Also known as: QST
Group A: Painful CIPN GroupGroup B: Control Group

-Immersion of a hand up to the wrist to a thermostat-controlled water bath maintained at 12 degrees Celsius, and the application of a heat stimulus on the contralateral forearm.

Also known as: CPM
Group A: Painful CIPN GroupGroup B: Control Group

-The subjects are asked to rate the intensity of their current pain on a 0-10 scale - 0 denoting "no pain" and 10 denoting "worst imaginable pain".

Group A: Painful CIPN GroupGroup B: Control Group

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Group A: Painful CIPN group
  • Age \>18
  • Distal symmetric pain distribution (both feet, with or without pain in hands).
  • The pain appeared during or up to 12 weeks after treatment with oxaliplatin, cisplatin, paclitaxel, docetaxel or any combination of these.
  • Score of 4 or more on Douleur Neuropathique 4 (DN4) neuropathic pain questionnaire
  • Pain duration \> 2 months.
  • Patient report of average daily pain intensity in the last week ≥3 on 0-10 Numerical Rating Scale (NRS).
  • Able and willing to sign an Institutional Review Board (IRB)-approved written informed consent.
  • Group B: Control group:
  • Age \>18
  • History of cancer diagnosis, previously treated with at least 8 infusions of chemotherapy regimen that included oxaliplatin or at least 6 infusions of chemotherapy regimen that included cisplatin, paclitaxel, docetaxel, or any combination of these.
  • No ongoing pain in distal symmetric distribution (subjects with symptoms and signs such as mild numbness, or vibration sensation loss are eligible to be included in the control group).
  • Able and willing to sign an IRB-approved written informed consent. \* Subjects in the control group will be matched by the type of previous chemotherapy to the subjects in the Painful CIPN group. An additional attempt will be made to match controls by sex, age, cancer diagnosis, and cumulative neurotoxic chemotherapy dose.

You may not qualify if:

  • History of pre-existing painful distal symmetric polyneuropathy prior to chemotherapy.
  • Alternative etiology exists for the distal painful symptoms.
  • Current or previous treatment with a vinca alkaloid (e.g. vincristine, vinblastine), bortezomib, or another agent which may cause major peripheral neurotoxicity.
  • Pregnant
  • Concomitant medication as follows:
  • Patients receiving chronic daily opioids, topical lidocaine or topical capsaicin will be excluded.
  • Patients receiving as needed (PRN) analgesics, including acetaminophen, NSAIDs or short-acting opioids, will be required not to take them 48h before testing, at for at least five half-lives of the specific analgesic, at the discretion of the investigators.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Publications (1)

  • Nemenov MI, Alaverdyan H, Burk C, Roles K, Frey K, Yan Y, Kazinets G, Haroutounian S. Characterization of Patients With and Without Painful Peripheral Neuropathy After Receiving Neurotoxic Chemotherapy: Traditional Quantitative Sensory Testing vs C-Fiber and Adelta-Fiber Selective Diode Laser Stimulation. J Pain. 2022 May;23(5):796-809. doi: 10.1016/j.jpain.2021.11.011. Epub 2021 Dec 9.

Related Links

MeSH Terms

Conditions

NeuralgiaPeripheral Nervous System Diseases

Interventions

4-amino-4'-hydroxylaminodiphenylsulfone

Condition Hierarchy (Ancestors)

Neuromuscular DiseasesNervous System DiseasesPainNeurologic ManifestationsSigns and SymptomsPathological Conditions, Signs and Symptoms

Results Point of Contact

Title
Simon Haroutounian, PhD. Assistant Professor,
Organization
Washington University

Study Officials

  • Simon Haroutounian, Ph.D.

    Washington University School of Medicine

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
NONE
Purpose
DIAGNOSTIC
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 25, 2018

First Posted

September 27, 2018

Study Start

September 17, 2018

Primary Completion

September 17, 2019

Study Completion

September 17, 2019

Last Updated

May 19, 2021

Results First Posted

October 22, 2020

Record last verified: 2021-04

Data Sharing

IPD Sharing
Will share

In accordance with the recent proposal from the International Committee of Medical Journal Editors, patient-level data will be made available within 6 months after publication of the primary manuscript. Data will be provided to researchers who submit a methodologically sound research proposal including a protocol and statistical analysis plan. No patient-identifying fields (including dates) will be included in the shared dataset. Certain technical data related to the intellectual property rights of LasMed LLC may not be available for sharing.

Shared Documents
STUDY PROTOCOL, ICF
Time Frame
Patient-level data will be made available within 6 months after publication of the primary manuscript.
Access Criteria
Data will be provided to researchers who submit a methodologically sound research proposal including a protocol and statistical analysis plan. No patient-identifying fields (including dates) will be included in the shared dataset. Certain technical data related to the intellectual property rights of LasMed LLC may not be available for sharing.

Locations