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

• ClinicalTrials.gov Identifier: NCT04393363
• Recruitment Status: Active, not recruiting
• First Posted: May 19, 2020
• Last Update Posted: February 2, 2023
• Sponsor: Aalborg University Hospital
• Collaborator: Aalborg University
• Information provided by (Responsible Party): Marianne Tang Severinsen, Aalborg University Hospital

Study Description

Brief Summary:

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.

Condition or disease
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 Design

• Study Type: Observational
• Estimated Enrollment: 20 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Early Detection and Prevention of Neuropathy and Cognitive Impairment Following Treatment for Haematological Malignancies (the NOVIT Study)
• Actual Study Start Date: August 14, 2020
• Estimated Primary Completion Date: June 30, 2023
• Estimated Study Completion Date: December 31, 2030

Groups and Cohorts

Outcome Measures

Primary Outcome Measures :

1. Change in neuropathy assessed by change in the neurotoxicity (ntx)-subscale of the FACT/GOG-Ntx-13-Score [ Time Frame: 0-12 months ]
   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

Secondary Outcome Measures :

1. Change in nerve excitability assessed by Perception Threshold Tracking [ Time Frame: 0-12 months ]
   Assessment of nerve excitability in both large and small fiber nerves measured by two different electrodes.
2. Change in The National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) [ Time Frame: 0-12 months ]
   A grading scale 1-5 (with 5 as the worst) for neuropathy evaluated by the medical doctor based on the patients' symptoms.
3. Change in the Total Neuropathy Score-Clinical [ Time Frame: 0-12 months ]
   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.
4. Change in Quality of Life (The total FACT/GOG-Ntx-score) [ Time Frame: 0-12 months ]
   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
5. Change in Montreal Cognitive Assessment (MoCA) [ Time Frame: 0-12 months ]
   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).
6. Change in the score for FACT/GOG-cog [ Time Frame: 0-12 months ]
   A patient questionnaire used to assess cognitive function. The score is measured from 0-132 with higher score meaning better Quality of Life
7. Change in VagusTM Test [ Time Frame: 0-12 months ]
   A measurement for autonomic neuropathy by evaluation of heart rate in different positions
8. Change in Bioimpendance [ Time Frame: 0-12 months ]
   Measurement of body composition in order to investigate loss of muscle mass, which can influence motor function and imitate or mask motor neuropathy
9. Change in vitamin B12-level in blood test [ Time Frame: 0-12 months ]
   Measurement of deficiency/functional deficiency

Biospecimen Retention:   Samples With DNA

Blood/plasma

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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.

Criteria

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

Contacts and Locations

Locations

Denmark

Department of Haematology, Aalborg University Hospital

Aalborg, Denmark, 9000

Sponsors and Collaborators

Aalborg University Hospital

Aalborg University

Investigators

• Principal Investigator: Marianne T Severinsen, MD, PhD; Aalborg University Hospital

More Information

• Responsible Party: Marianne Tang Severinsen, Consultant, Head of Research, Ass. Professor, Aalborg University Hospital
• ClinicalTrials.gov Identifier: NCT04393363
• Other Study ID Numbers: N-20190068
• First Posted: May 19, 2020
• Last Update Posted: February 2, 2023
• Last Verified: February 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Marianne Tang Severinsen, Aalborg University Hospital:

vincristine; bortezomib; lenalidomide; Assessment of nerve fiber excitability

Additional relevant MeSH terms:

Hematologic Neoplasms; Peripheral Nervous System Diseases; Cognitive Dysfunction; Neoplasms; Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Neuromuscular Diseases; Nervous System Diseases; Neoplasms by Site; Hematologic Diseases