Early Detection of Neuropathy and Cognitive Impairment Following Treatment for Haematological Malignancies (NOVIT1)

Early Detection and Prevention of Neuropathy and Cognitive Impairment Following Treatment for Haematological Malignancies (the NOVIT Study)

Chemotherapy-induced peripheral neuropathy (CIPN) is a common, but not well understood complication to treatment with chemotherapy. In this study the investigators will investigate a novel method for early detection of CIPN and compare it to other methods in patients treated for haematological cancers.

Study Overview

• Status: Active, not recruiting
• Conditions: Chemotherapy-induced Peripheral Neuropathy

Detailed Description

Haematological malignancies can be treated with chemotherapy if the patient tolerates the treatment. However, many patients develop complications during treatment including chemotherapy-induced peripheral neuropathy (CIPN) and/or impaired memory. Even though it is a well-known complication, no gold standard for CIPN assessment is known. Besides chemotherapy reduction or cessation, there is so far no sufficient prevention or treatment, therefore early detection and intervention is crucial.

The main purpose of this study is to find a reliable test for chemotherapy-induced peripheral neuropathy (CIPN) in order to predict early signs of CIPN. All included patients has to be scheduled for treatment with vincristine, bortezomib or lenalidomide regardless of haematological malignancy. Neuropathy and cognitive impairment will be tested at baseline (prior to treatment with chemotherapy), before each treatment course, 1 month after treatment and finally 1 year after onset of chemotherapy. CIPN will be examined by different methods: Clinician-based assessment, objective neurophysiological parameters and patient-reported outcome. A novel test using Perception Threshold Tracking (PTT), developed at Aalborg University, is included in the study. The test investigates the nerve excitability in both large and small fiber nerve fibers using two different electrodes. Blood samples will be collected, stored, and analyzed for deficiencies correlated to neuropathy.

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

Contacts and Locations

• Study Contact: Name: Marianne T Severinsen, MD, PhD; Phone Number: +45 97663861; Email: m.severinsen@rn.dk
• Study Contact Backup: Name: Eva F Maksten, MD; Email: efm@rn.dk

Study Locations

• Denmark
  • Aalborg, Denmark, 9000
    • Department of Haematology, Aalborg University Hospital

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Haematological patients scheduled for (but not started) treatment with vincristine, bortezomib or lenalidomid regardless of type of haematological malignancy.

Description

Inclusion Criteria:

• Men and women, age ≥ 18 years
• Scheduled for treatment with Vincristine (R-CHOP, CHOP, R-CHOEP, CHOEP, R-CVP, CVP or simi-lar), Bortezomib (VCD, MPV, VRD or similar) or Lenalidomide (VRD, len-dex or similar) regardless of type of haematological malignancy
• Not started chemotherapy treatment before enrollment (pretreatment with steroids is allowed)
• Associated to Department of Haematology, Aalborg University Hospital during the project period
• Signed informed consent form
• Able to read and speak Danish

Exclusion Criteria:

• Known vitamin B12 deficiency and treated with either oral or intramuscular vitamin B12 within the last year
• Known neural damage or disease in the neural system (e.g. MS, Guillain-Barre etc.)
• Known severe skin disease
• Pregnancy or breastfeeding
• Inability to understand or comply with instructions

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in neuropathy assessed by change in the neurotoxicity (ntx)-subscale of the FACT/GOG-Ntx-13-Score	A patient questionnaire with focus on Quality of Life and neuropathy. Range 0-52 with higher score meaning better Quality of Life (less neuropathy). Neuropathy will be defined as a 10 % reduction in the Ntx-score	0-12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in nerve excitability assessed by Perception Threshold Tracking	Assessment of nerve excitability in both large and small fiber nerves measured by two different electrodes.	0-12 months
Change in The National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE)	A grading scale 1-5 (with 5 as the worst) for neuropathy evaluated by the medical doctor based on the patients' symptoms.	0-12 months
Change in the Total Neuropathy Score-Clinical	A score based on clinical evaluation (pin and vibration sensibility, strength and reflexes) and subjective reports from the patient (sensory, motor and autonomic symptoms). The score grades from 0-28 with 28 at worst.	0-12 months
Change in Quality of Life (The total FACT/GOG-Ntx-score)	A patient questionnaire with focus on Quality of Life and neuropathy. This part will focus on Quality of Life. Score range from 0-160 with higher score meaning higher Quality of Life	0-12 months
Change in Montreal Cognitive Assessment (MoCA)	A quick and easy method to assess mild cognitive disturbance based on following parameters: Awareness, concentration, executive function, memory, abstract thinking, calculating abilities and orientation. The score is 0-30, score > 26 is normal (without cognitive disturbance).	0-12 months
Change in the score for FACT/GOG-cog	A patient questionnaire used to assess cognitive function. The score is measured from 0-132 with higher score meaning better Quality of Life	0-12 months
Change in VagusTM Test	A measurement for autonomic neuropathy by evaluation of heart rate in different positions	0-12 months
Change in Bioimpendance	Measurement of body composition in order to investigate loss of muscle mass, which can influence motor function and imitate or mask motor neuropathy	0-12 months
Change in vitamin B12-level in blood test	Measurement of deficiency/functional deficiency	0-12 months

Collaborators and Investigators

• Sponsor: Aalborg University Hospital
• Collaborators: Aalborg University
• Investigators: Principal Investigator: Marianne T Severinsen, MD, PhD, Aalborg University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 14, 2020
• Primary Completion (Actual): August 30, 2023
• Study Completion (Estimated): December 31, 2030

Study Registration Dates

• First Submitted: May 14, 2020
• First Submitted That Met QC Criteria: May 18, 2020
• First Posted (Actual): May 19, 2020

Study Record Updates

• Last Update Posted (Estimated): January 31, 2024
• Last Update Submitted That Met QC Criteria: January 30, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: lenalidomide; bortezomib; vincristine; Assessment of nerve fiber excitability
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neoplasms; Neoplasms by Site; Neurocognitive Disorders; Hematologic Diseases; Neuromuscular Diseases; Cognition Disorders; Hematologic Neoplasms; Peripheral Nervous System Diseases; Cognitive Dysfunction
• Other Study ID Numbers: N-20190068

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: No
• Studies a U.S. FDA-regulated device product: No