Trial Outcomes & Findings for Chronic Neuropathy Following Chemotherapy (NCT NCT02654691)

NCT ID: NCT02654691

Last Updated: 2021-02-25

Results Overview

For case definition of neuropathy, The Toronto classification (Tesfaye et al. 2010) will be used. Numbers indicate confirmed neuropathy.

• Recruitment status: COMPLETED
• Target enrollment: 63 participants
• Primary outcome timeframe: 5-year follow-up
• Results posted on: 2021-02-25

Participant Flow

Participant milestones

Measure	Chemotherapy Patients treated with docetaxel or oxaliplatin.
Overall Study STARTED	63
Overall Study COMPLETED	63
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	Chemotherapy n=63 Participants Patients treated with docetaxel or oxaliplatin.
Age, Categorical <=18 years	0 Participants n=63 Participants
Age, Categorical Between 18 and 65 years	36 Participants n=63 Participants
Age, Categorical >=65 years	27 Participants n=63 Participants
Age, Continuous	63.6 years STANDARD_DEVIATION 9.1 • n=63 Participants
Sex: Female, Male Female	40 Participants n=63 Participants
Sex: Female, Male Male	23 Participants n=63 Participants
Region of Enrollment Denmark	63 participants n=63 Participants

PRIMARY outcome

Timeframe: 5-year follow-up

For case definition of neuropathy, The Toronto classification (Tesfaye et al. 2010) will be used.

Numbers indicate confirmed neuropathy.

Outcome measures

Measure	Chemotherapy n=63 Participants Patients treated with docetaxel or oxaliplatin.
Chemotherapy-induced Peripheral Neuropathy	21 participants

PRIMARY outcome

Timeframe: 5-year follow-up

Neuropathic pain grading system. Neuropathic pain was graded as "possible", "probable", or "definite" in accordance with the NeuPSIG grading system (Pascal M et al, Wellcome Open Research 2018).

Outcome measures

Measure	Chemotherapy n=63 Participants Patients treated with docetaxel or oxaliplatin.
Chemotherapy-induced Neuropathic Pain	19 Participants

SECONDARY outcome

Timeframe: 5-year follow-up

Population: Patients with an abnormal value indicating loss of function

Modified German Research Network on Neuropathic Pain QST protocol assessed sensory abnormalities after chemotherapy assessed with quantitative sensory testing (QST).

Outcome measures

Measure	Chemotherapy n=62 Participants Patients treated with docetaxel or oxaliplatin.
Sensory Abnormalities After Chemotherapy Assessed With Quantitative Sensory Testing (QST). Abnormal mechanical detection threshold	11 participants
Sensory Abnormalities After Chemotherapy Assessed With Quantitative Sensory Testing (QST). Abnormal paradoxical heat sensation	16 participants
Sensory Abnormalities After Chemotherapy Assessed With Quantitative Sensory Testing (QST). Abnormal mechanical pain threshold	8 participants
Sensory Abnormalities After Chemotherapy Assessed With Quantitative Sensory Testing (QST). Abnormal thermal detection	11 participants
Sensory Abnormalities After Chemotherapy Assessed With Quantitative Sensory Testing (QST). Abnormal vibration detection	18 participants

SECONDARY outcome

Timeframe: 5-year follow-up

Population: Sensory recordings from participants, the relative refractory period

Measurements found with threshold tracking. The most common sensory parameters assessed with sensory threshold tracking. Outcomes are extracted from the QTrack software. The relative refractory period (RRP) is the interval of time during which a second action potential can be initiated, refractoriness is change in threshold by a preceding simple impulse, and specifically at 2,5 ms. A shorten RRP makes the nerve more excitable and longer RRP less excitable (values see result 21 for refractoriness at 2.5 ms, superexcitability and subexcitability).

Outcome measures

Measure	Chemotherapy n=55 Participants Patients treated with docetaxel or oxaliplatin.
Neuronal Excitability Changes After Chemotherapy Assessed With Threshold Tracking: Sensory	3.1 ms Standard Error 1.0

SECONDARY outcome

Timeframe: 5-year follow-up

Number of patients with mild, moderate or severe symptoms of depression or anxiety. Patient Reported Outcomes Measurement Information System (PROMIS) used to assess if the patients has a mild, moderat or severe symptoms of depression/anxiety. The scores from the questionnaires were converted into T-scores, which were used in grading the patients with mild , moderate or severe symptoms of depression or anxiety. A higher score indicates worse outcome. The minimum is no depression or anxiety and the maximum is severe depression or anxiey. Mild: T-score ≥55 and <65 Moderate: ≥65 and <75 Severe ≥75

Outcome measures

Measure	Chemotherapy n=63 Participants Patients treated with docetaxel or oxaliplatin.
Anxiety and Depression Using the Patient Reported Outcomes Measurement Information System (PROMIS). Anxiety	12 participants
Anxiety and Depression Using the Patient Reported Outcomes Measurement Information System (PROMIS). Depression	12 participants
Anxiety and Depression Using the Patient Reported Outcomes Measurement Information System (PROMIS). Anxiety or Depression	16 participants

SECONDARY outcome

Timeframe: 5-year follow-up

Mean scores using HADS of all participants. The score for anxiety and depression indicate the sum of 7 questions, each graded from 0 to 3. This means that a person can score between 0 (minimum) and 21 (maximum) for either anxiety or depression. Higher score meaning more symptoms of a possible depression or anxiety.

Outcome measures

Measure	Chemotherapy n=63 Participants Patients treated with docetaxel or oxaliplatin.
Anxiety and Depression Using the Hospital Anxiety and Depression Scale (HADS). Anxiety	4.38 score on a scale Standard Deviation 3.76
Anxiety and Depression Using the Hospital Anxiety and Depression Scale (HADS). Depression	2.40 score on a scale Standard Deviation 2.34

SECONDARY outcome

Timeframe: 5-year follow-up

Population: Numbers given is patients with mild, moderate or severe fatigue.

Number of patients with mild, moderate or severe fatigue. PROMIS used to assess if the patients has a mild, moderat or severe symptoms of fatique. The scores from the questionnaires were converted into T-scores, which were used in grading the patients with mild, moderate or severe symptoms of fatigue. The minimum is no fatigue (T-score<50) and maximum severe fatigue (T-score ≥75). Higher scores mean a worse outcome. Mild: T-score ≥55 and <65 Moderate: ≥65 and <75 Severe ≥75

Outcome measures

Measure	Chemotherapy n=63 Participants Patients treated with docetaxel or oxaliplatin.
Fatigue Using the Patient Reported Outcomes Measurement Information System (PROMIS).	25 Participants

SECONDARY outcome

Timeframe: 5-year follow-up

The participants were asked to provided a score from 1-100 regarding quality of life on the Quality of life using EuroQol (EQ-5D). Minimum score 0, maximum score 100. A higher score indicate better outcome

Outcome measures

Measure	Chemotherapy n=63 Participants Patients treated with docetaxel or oxaliplatin.
Quality of Life Using EuroQol (EQ-5D).	78.4 units on a scale Standard Deviation 17.2

SECONDARY outcome

Timeframe: 5-year follow-up

Population: Answers are missing for 1 participant.

The Personality using the 10-item Personality Inventory (TIPI). TIPI is divided in 5 parameters Extraversion, Agreeableness, Conscientiousness, Emotional Stability, Openness. Minimum value is 2 and maximum value i 14. Higher scores indicate more Openness, Conscientiousness, Extraversion, Agreeableness and Emotional Stability

Outcome measures

Measure	Chemotherapy n=62 Participants Patients treated with docetaxel or oxaliplatin.
Personality Using the 10-item Personality Inventory (TIPI). Extraversion	4.5 units on a scale Standard Deviation 1.5
Personality Using the 10-item Personality Inventory (TIPI). Agreeableness	4.9 units on a scale Standard Deviation 1.1
Personality Using the 10-item Personality Inventory (TIPI). Conscientiousness	5.2 units on a scale Standard Deviation 1.1
Personality Using the 10-item Personality Inventory (TIPI). Emotional Stability	5.2 units on a scale Standard Deviation 1.3
Personality Using the 10-item Personality Inventory (TIPI). Openness	5.3 units on a scale Standard Deviation 1.1

SECONDARY outcome

Timeframe: 5-year follow-up

Population: Results from 1 participant were missing

Personality using the International Personality Item Pool (IPIP). A score were given from answering 10 questions regarding emotionel stability. Each question has 5 possible answers from 1 very inaccuate to 5 very accurate. Minimum combined value 10, maximum combined value 50. Higher score indicates worse outcome.

Outcome measures

Measure	Chemotherapy n=62 Participants Patients treated with docetaxel or oxaliplatin.
Personality Using the International Personality Item Pool (IPIP).	34.3 score on a scale Standard Deviation 7.6

SECONDARY outcome

Timeframe: 5-year follow-up

Participants answered 13 question, which were each graded on a scale from 0-4 and combined to a sum scale.. The results are a mean score for all participants. The minimum value is 0 and the maximum value is 72. Higher scores indicate more Pain catastrophizing.

Outcome measures

Measure	Chemotherapy n=63 Participants Patients treated with docetaxel or oxaliplatin.
Pain Catastrophizing Using the Pain Catastrophizing Scale(PCS).	7.6 score on a scale Standard Deviation 9.4

SECONDARY outcome

Timeframe: 5-year follow-up

Population: Missing data in 10 patients

The fibers in the cornea were scanned in one eye with the Heidelberg Retina Tomograph III laser-scanning confocal microscope (Heidelberg Engineering GmbH, Heidelberg, Germany). An automatic programme calculated the cornea nerve branches density (CNBD) and the cornea nerve fiber density (CNFD).

Outcome measures

Measure	Chemotherapy n=53 Participants Patients treated with docetaxel or oxaliplatin.
Morphology of Small Fibers in Cornea After Chemotherapy by Corneal Confocal Microscopy (CCM). CNBD	30.5 units/mm2 Standard Deviation 13.5
Morphology of Small Fibers in Cornea After Chemotherapy by Corneal Confocal Microscopy (CCM). CNFD	22.8 units/mm2 Standard Deviation 7.8

SECONDARY outcome

Timeframe: 5-year follow-up

Population: Numbers indicate the number of participants, who had a blood sample collected. Not analyzed separately

Numbers indicate the number of participants, who had a blood sample collected. Potential gene associations in the development of painful neuropathy will be assessed together with other samples in the DOLORisk collaboration. The results here present the number of subjects who had a DNA blood sample taken.

Outcome measures

Measure	Chemotherapy n=63 Participants Patients treated with docetaxel or oxaliplatin.
Blood Samples DNA	58 participants

SECONDARY outcome

Timeframe: 5-year follow-up

Population: Of the 63 included in the study, 19 patients had symptoms of neuropathic pain. Numbers given is patients with mild, moderate or severe pain interference of the patients with neuropathic pain.

Numbers given is patients with mild, moderate or severe pain interference of the patients with neuropathic pain. Patient Reported Outcomes Measurement Information System PROMIS used to assess if the patients has a mild, moderate or severe symptoms of pain interference. The scores from the questionnaires were converted into T-scores, which were used in grading the patients with mild, moderate or severe pain interference. The mimimum is no interference (T-score <50) and maximum is Severe (T-score≥70)). Severe indicated more interference

Outcome measures

Measure	Chemotherapy n=19 Participants Patients treated with docetaxel or oxaliplatin.
Pain Interference by Patient Reported Outcomes Measurement Information System (PROMIS).	17 Participants

SECONDARY outcome

Timeframe: 5-Year follow-up

Population: Of the 63 included in the study, 19 patients had symptoms of neuropathic pain. The result are the number of participants with a possible painful neuropathy with the DN4.

number of participants with a possible painful neuropathy with the Douleur Neuropathique 4DN4. Yes/no questions regarding symptoms and signs of neuropathic pain. In total the participants answered 7 questions. Each question is a yes or no and are combined to a sum score of number of positive answers. Minimum score is 0 and maximum score is 7. Higher score indicates larger probability of neuropathic Pain. A score of 3 or above indicates a possible painful neuropathy.

Outcome measures

Measure	Chemotherapy n=19 Participants Patients treated with docetaxel or oxaliplatin.
Pain Descriptors by Douleur Neuropathique 4 (DN4).	13 Participants

SECONDARY outcome

Timeframe: 5-Year follow-up

Population: Of the 63 included in the study, 19 patients had symptoms of neuropathic pain. The result are the score of participants with a neuropathic pain.

The results were given on a scale from 0-100 for each of the 5 dimensions on the Neuropathic Pain Symptom Inventory (NPSI). Higher scores indicate worse symptoms. The sum score is the sum divided by 5. Minimum score is 0 and maximum score is 100.

Outcome measures

Measure	Chemotherapy n=19 Participants Patients treated with docetaxel or oxaliplatin.
Pain Descriptors by Neuropathic Pain Symptom Inventory (NPSI).	23.3 score on a scale Standard Deviation 20.9

SECONDARY outcome

Timeframe: 5-year follow-up

Population: Results wer missing in 4 participants.

The Toronto Clinical Scoring System(TCSS), grades the severity of neuropathy and consists of 6 questions with the presence and description of symptoms and a 7-item clinical examination with reflexes in the lower extremities and a bedside sensory testing with pinprick, vibration, temperature, light touch and position of the 1st toe. The score ranges from 0-19. Higher score indicate worse outcome.

Outcome measures

Measure	Chemotherapy n=59 Participants Patients treated with docetaxel or oxaliplatin.
Neuropathy Using the Toronto Clinical Scoring System (TCSS).	4.8 score on a scale Standard Deviation 3.2

SECONDARY outcome

Timeframe: 5-year follow-up

Population: The results were missing for 5 participants.

The TNScompact consists of 7 questions regarding sensory symptoms, motor symptoms, autonomic symptoms, pin sensation, vibrations sensitivity, strength and tendon reflexes graded from 0-4. The scores are combined and thus 0 being the lowest score possible and 28 being the highest score possible. A high score indicate severe neuropathy.

Outcome measures

Measure	Chemotherapy n=58 Participants Patients treated with docetaxel or oxaliplatin.
Neuropathy Using the Total Neuropathy Score.	3.9 score on a scale Standard Deviation 3.0

SECONDARY outcome

Timeframe: 5-year follow-up

A cut-off ≥ 4/13 abnormal responses has been suggested as the cut-off to define polyneuropathy.

Outcome measures

Measure	Chemotherapy n=63 Participants Patients treated with docetaxel or oxaliplatin.
Neuropathy Using the Michigan Neuropathy Screening Instrument (MNSI).	21 Participants

SECONDARY outcome

Timeframe: 5-year follow-up

Population: Motor recordings from participants, relative refractory period

Measurements found with threshold tracking. The most common motor parameters assessed with threshold tracking. Outcomes are extracted from the QTrack software. The relative refractory period (RRP) is the interval of time during which a second action potential can be initiated, refractoriness is change in threshold by a preceding simple impulse, and specifically at 2,5 ms. A shorten RRP makes the nerve more excitable and longer RRP less excitable (values see result 22 for refractoriness at 2.5 ms, superexcitability and subexcitability).

Outcome measures

Measure	Chemotherapy n=60 Participants Patients treated with docetaxel or oxaliplatin.
Neuronal Excitability Changes After Chemotherapy Assessed With Threshold Tracking: Motor	3.0 ms Standard Error 1.0

SECONDARY outcome

Timeframe: 5-year follow-up

Population: Sensory recordings from participants, refractoriness at 2.5 ms, superexcitability and subexcitability

Measurements found with threshold tracking. The most common sensory parameters assessed with sensory threshold tracking. Outcomes are extracted from the QTrack software. The relative refractory period (RRP) is the interval of time during which a second action potential can be initiated, refractoriness is change in threshold by a preceding simple impulse, and specifically at 2,5 ms. A shorten RRP makes the nerve more excitable and longer RRP less excitable (values see result 21 for refractoriness at 2.5 ms, superexcitability and subexcitability). Superexcitability and subexcitablity are measured in the recovery period. The recovery cycle is characterized by changes in axonal excitability following a supramaximal conditioning stimulus. The cycle includes a relative refractory period (at short inter-stimulus intervals), superexcitable period (when the threshold is reduced), and subexcitable period (when the nerve is less excitable).

Outcome measures

Measure	Chemotherapy n=55 Participants Patients treated with docetaxel or oxaliplatin.
Neuronal Excitability Changes After Chemotherapy Assessed With Threshold Tracking: Sensory Refractoriness at 2.5 ms	11.0 percentage of 100% Standard Error 1.9
Neuronal Excitability Changes After Chemotherapy Assessed With Threshold Tracking: Sensory Superexcitability	17.4 percentage of 100% Standard Error 0.8
Neuronal Excitability Changes After Chemotherapy Assessed With Threshold Tracking: Sensory Subexcitability	10.9 percentage of 100% Standard Error 0.8

SECONDARY outcome

Timeframe: 5-year follow-up

Population: Motor recordings from participants, refractoriness at 2.5 ms, superexcitability and subexcitability

Measurements found with threshold tracking. The most common motor parameters assessed with threshold tracking. Outcomes are extracted from the QTrack software. The relative refractory period (RRP) is the interval of time during which a second action potential can be initiated, refractoriness is change in threshold by a preceding simple impulse, and specifically at 2,5 ms. A shorten (RRP) makes the nerve more excitable and longer RRP less excitable (values see result 22 for refractoriness at 2.5 ms, superexcitability and subexcitability). Superexcitability and subexcitablity are measured in the recovery period. The recovery cycle is characterized by changes in axonal excitability following a supramaximal conditioning stimulus. The cycle includes a relative refractory period (at short inter-stimulus intervals), superexcitable period (when the threshold is reduced), and subexcitable period (when the nerve is less excitable).

Outcome measures

Measure	Chemotherapy n=60 Participants Patients treated with docetaxel or oxaliplatin.
Neuronal Excitability Changes After Chemotherapy Assessed With Threshold Tracking: Motor Refractoriness at 2.5 ms	18.8 percentage of 100% Standard Error 1.9
Neuronal Excitability Changes After Chemotherapy Assessed With Threshold Tracking: Motor Superexcitability	21.8 percentage of 100% Standard Error 0.8
Neuronal Excitability Changes After Chemotherapy Assessed With Threshold Tracking: Motor Subexcitability	16.2 percentage of 100% Standard Error 0.7

Adverse Events

Chemotherapy

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Nanna Finnerup

Aarhus University

Phone: 0045 78463382

Email: finnerup@clin.au.dk

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place