Memantine XR and Pregabalin for Chemotherapy-Induced Peripheral Neuropathy

An Observational Study Efficacy and Safety of Memantine XR (Extended Release) and Pregabalin Combination Therapy in Chemotherapy-Induced Peripheral Neuropathy (CIPN)

Study is designed to assess the efficacy and safety of memantine XR and pregabalin in reducing neuropathic pain in patients with chemotherapy-induced peripheral neuropathy (CIPN) caused by prior treatment with any chemotherapy as measured by the Brief Pain Inventory- Short Form (BPI-SF). It will also determine the influence of these drugs on peripheral neuropathy-related functional status and quality of life (QOL) as measured by the EORTC QLQ-C30.

Study Overview

• Status: Completed
• Conditions: Chemotherapy-induced Peripheral Neuropathy
• Intervention / Treatment: Drug: Memantine XR-pregabalin combination therapy

Detailed Description

Using an observational, case-only, prospective design, potential subjects will be identified from patients with chemotherapy induced peripheral neuropathy (CIPN) that are planning to be treated with memantine XR-pregabalin combination therapy. The primary objective is to assess the efficacy of memantine XR and pregabalin in reducing neuropathic pain as measured by the Brief Pain Inventory- Short Form (BPI-SF). Patients who agree to participate will be asked to complete study questionnaires prior to the start of their CIPN treatment and once per week for six weeks during their treatment. After this period, patients will be contacted once per month for three months to assess interval medical history, concomitant medications, and adverse events.

• Study Type: Observational
• Enrollment (Actual): 20

Contacts and Locations

Study Locations

• United States
  • California
    • Santa Monica, California, United States, 90404
      • John Wayne Cancer Institute at Providence Saint John's Health Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with chemotherapy induced peripheral neuropathy (CIPN) that are planning to be treated with memantine XR-pregabalin combination therapy

Description

Inclusion Criteria:

Ability to understand and the willingness to sign a written informed consent. History of any type of cancer treated with chemotherapy.

Chemotherapy induced peripheral neuropathy (CIPN) due to:

• Cisplatin, carboplatin, and oxaliplatin
• Taxanes- paclitaxel, docetaxel, and cabazitaxel
• Thalidomide, lenalidomide, and pomalidomide
• Plant alkaloids, such as vinblastine, vincristine, vinorelbine, and etoposide
• Epothilones, such as ixabepilone
• Bortezomib, carfilzomib
• Eribulin Planning to receive treatment for CIPN with memantine XR and pregabalin. Average daily neuropathic pain intensity > 4 measured by item #5 of BPI-SF (Average daily pain at baseline is the average of pain scores over the last 7 days before enrolling patients in to the study).

CIPN > grade 1 as measured by NCI-CTCAE v 4.0. Must be ≥ 3 months beyond completion of chemotherapy. Not planning to receive concurrent chemotherapeutic agents during the study period.

Patients with diabetes mellitus, peripheral vascular disease, HIV infection, or a significant degenerative or familial neurologic can be included in the study provided they don't have peripheral neuropathy secondary to above mentioned diseases.

Allowable types and amount of prior therapy for neuropathy:

• Patients receiving analgesics for pain associated with CIPN are eligible provided they have taken the same dosage and same medication for at least 2 weeks prior to the study initiation.
• Patients on antidepressants regimens of Selective Serotonin Reuptake Inhibitors (SSRI) or Selective serotonin norepinephrine reuptake inhibitors (SSNRI) for treatment of anxiety or depression, anticonvulsants or mexiletine for the treatment of pain are eligible provided they are on stable dose for 30 days.

Age ≥ 18 years. Both men and women of all races and ethnic groups are eligible for this trial.

Exclusion Criteria:

Any pain other than neuropathic pain of equal or greater severity. Patients with sensory polyneuropathy due to AIDS/HIV, complex regional pain syndrome, and Trigeminal neuralgia.

History of suicidal ideation. Patients with a history of non-compliance. Patients who are judged by the investigator to be unable or unlikely to understand the nature, scope, and possible consequences of the study.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Observation Group; Subjects will be identified from patients with chemotherapy induced peripheral neuropathy (CIPN) that are planning to be treated with memantine XR-pregabalin combination therapy.Patients who agree to participate will be asked to complete study questionnaires prior to the start of their CIPN treatment and once per week for six weeks during their treatment.	Drug: Memantine XR-pregabalin combination therapy; Pregabalin and memantine XR work in different pathways and are approved by the U.S. Food and Drug Administration for various indications. Both medications have an established safety profile and have demonstrated improvement on neuropathy-related symptoms.; Other Names: Namenda XR-Lyrica

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in average daily pain intensity as measured by the Brief Pain Inventory- Short Form (BPI-SF)	Absolute change in the average daily pain intensity as measured by the Brief Pain Inventory- Short Form (BPI-SF) from baseline to the end of 6 weeks measured by item # 5 of Brief Pain Inventory Score (BPI-SF). The BPI assesses pain at its "worst," "least," "average," and "now" (current pain). In clinical trials, the items "worst" and "average" have each been used singly to represent pain severity. A composite of the four pain items (a mean severity score) is sometimes presented as supplemental information.	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in quality of life (QOL) as measured by European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30 (EORTC QLQ-C30)	Absolute change in the QoL measured by European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30 (EORTC QLQ-C30) after 6 weeks of treatment compared to baseline. The QLQ-C30 is composed of both multi-item scales and single-item measures. These include five functional scales, three symptom scales, a global health status / QoL scale, and six single items. Each of the multi-item scales includes a different set of items - no item occurs in more than one scale. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.	6 weeks
Change in the intensity of mechanical allodynia measured using qualitative sensory testing	Absolute change in mechanical allodynia intensity after 6 weeks of treatment compared to baseline. Testing is done by touching the sensitive (neuropathic) area with a foam brush 3 times in 5 secs and asking the patient about their pain score before and after the procedure.	6 weeks
Change in neuropathic symptoms as measured by Neuropathic Pain Symptom Inventory (NPSI)	Absolute change in neuropathic symptoms measured by Neuropathic Pain Symptom Inventory (NPSI) scores after 6 weeks of treatment compared to baseline. A total intensity score can be calculated as the sum of the scores of the 10 descriptors ranging from 0 to 100. Five subscores corresponding to the mean scores of the items belonging to each of the five dimensions ranging from 0 to 10. ) is "no pain" and 10 is "the most intense pain imaginable".	6 weeks
Change in reported sleep interference as measured by item # 9 of Brief Pain Inventory- Short Form (BPI-SF)	Absolute change in sleep interference measured by item # 9 of Brief Pain Inventory Score (BPI-SF) after 6 weeks of treatment from baseline. Score for question 9F for sleep ranges from 0 "does not interfere" to 10 "completely interferes".	6 weeks

Collaborators and Investigators

• Sponsor: Saint John's Cancer Institute

Study record dates

Study Major Dates

• Study Start (Actual): July 9, 2016
• Primary Completion (Actual): April 29, 2021
• Study Completion (Actual): April 29, 2021

Study Registration Dates

• First Submitted: July 10, 2018
• First Submitted That Met QC Criteria: October 16, 2018
• First Posted (Actual): October 17, 2018

Study Record Updates

• Last Update Posted (Actual): April 6, 2022
• Last Update Submitted That Met QC Criteria: April 5, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neuromuscular Diseases; Peripheral Nervous System Diseases; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Dopamine Agents; Anti-Anxiety Agents; Anticonvulsants; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Antiparkinson Agents; Anti-Dyskinesia Agents; Pregabalin; Memantine
• Other Study ID Numbers: JWCI-17-0101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No