Exploration by NMR Spectroscopy of the Choline Concentrations in the Insular Cortex of Patients Suffering of Neuropathic Pain Induced by Oxaliplatin - Clinical Trial for Neuropathy | NCT02340403

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Primary Purpose

Status

Completed

Phase

Not Applicable

Locations

France

Study Type

Interventional

Intervention

NMR Spectroscopy

About this trial

This is an interventional diagnostic trial for Neuropathy focused on measuring Neuropathy, Oxaliplatin, Insula, choline

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Oxaliplatin treated patient and suffering from neuropathic pain
- Chemotherapy (oxaliplatin based) ended
- Pain VAS ≥ 3/10, 1 month after the chemotherapy end
- DN4 interview score ≥ 3/7, 1 month after the chemotherapy end
Oxaliplatin treated patient without neuropathic pain
- Chemotherapy (oxaliplatin based) ended
- Pain VAS < 3/10, 1 month after the chemotherapy end
- DN4 interview score < 3/7, 1 month after the chemotherapy end
All patients
- right-handed
- No contrindication to MRI
- Free, written and informed consent
- Affiliated to the french health system
- Effective contraception for male or female of childbearing age
- Performance score (WHO) ≤ 2

Exclusion Criteria:

Age < 18
Left-handed
BMI > 30 kg/m²
Amputees of all or part of an upper limb
Diabetic patient
Painful events scheduled after enrollment (eg. surgical resection)
Neurological diseases (eg Parkinson's disease, stroke, migraine, fibromyalgia ...)
Chronic pain history before chemotherapy
Analgesic treatment being other than paracetamol and weak opioids
Alcohol consumption >3 units/day (30 g/day) for men and >2 units/day (20 g/day) for women
Any unbalanced progressive disease (hepatic failure, renal impairment (creatinine clearance <30 mL/min), respiratory failure, congestive heart failure, myocardial infarction within the past 6 months ...)
All active cancer
Patient with a pacemaker, a cochlear implant, metal implants, or any other magnetic element
Claustrophobia
Pregnant or lactation
Legal incapacity (person deprived of liberty or guardianship)
Psychological, social, family or geographical reasons incompatible with the study
Already included in another clinical trial

Sites / Locations

CHU de Clermont-Ferrand

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Other

Arm Label

Oxaliplatin and neuropathic pain

Oxaliplatin without neuropathic pain

Arm Description

The objective of this study is to demonstrate a significant increase in choline concentration in the insular cortex of patients with an oxaliplatin induced neuropathy. Other objectives will assess the correlation between metabolite concentrations in the insular cortex and frequency / intensity of pain and neuropathic symptoms, cold and heat-induced pain and comorbidities (anxiety, pain, quality of life).

Outcomes

Primary Outcome Measures

Choline concentration assessed by NMR spectroscopy in the posterior insula

Secondary Outcome Measures

Metabolite concentrations assessed by NMR spectroscopy in the posterior insula

Metabolite (choline, myo-inositol, N-acétylaspartate, créatine, glutamate/glutamine, lactate and taurine)

Pain intensity (VAS and BPI questionnaire)

(VAS and BPI questionnaire)

Neuropathic pain diagnostic 9DN4 interview questionnaire)

Neuropathic pain intensity (NPSI questionnaire)

NPSI questionnaire

BPI questionnaire

Quantitative sensory threshold (cold, heat, vibration)

Neuropathy grade

Anxiety and depression symptoms (HADS questionnaire)

HADS questionnaire

Intensity of chemotherapy-induced peripheral neuropathy (CIPN20 questionnaire)

CIPN20 questionnaire

Health related quality of life (QLQ-C30 questionnaire)

(QLQ-C30 questionnaire

Full Information

NCT ID

NCT02340403

First Posted

January 8, 2015

Last Updated

December 30, 2021

Sponsor

University Hospital, Clermont-Ferrand

1. Study Identification

Unique Protocol Identification Number

NCT02340403

Brief Title

Exploration by NMR Spectroscopy of the Choline Concentrations in the Insular Cortex of Patients Suffering of Neuropathic Pain Induced by Oxaliplatin

Acronym

INSULOX

Official Title

Exploration by NMR Spectroscopy of the Choline Concentrations in the Insular Cortex of Patients Suffering of Neuropathic Pain Induced by Oxaliplatin

Study Type

Interventional

2. Study Status

Record Verification Date

December 2021

Overall Recruitment Status

Completed

Study Start Date

March 9, 2014 (Actual)

Primary Completion Date

February 4, 2021 (Actual)

Study Completion Date

August 27, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University Hospital, Clermont-Ferrand

4. Oversight

5. Study Description

Brief Summary

Neurotoxic chemotherapy, including oxaliplatin, are responsible for very disabling neuropathic pain that can last for months or even years after the end of chemotherapy. Currently, there is no effective neuroprotective treatment to prevent or relieve this pain. The only strategy is the reduction of oxaliplatin doses or premature discontinuation of therapy, with the risk of burdening the prognosis for remission. Thus, a better understanding of the pathophysiology of these iatrogenic neuropathies appears necessary in order to discover new potential therapeutic targets. Preclinical works were able to demonstrate important metabolic changes in certain brain structures in an animal model of oxaliplatin-induced neuropathy. A significant increase of choline concentration has been found in the posterior insular cortex of neuropathic animals compared with control animals. Furthermore, the concentrations of choline were positively correlated to nociceptive thresholds. Thus, neuropathic pain induced by oxaliplatin would involve the posterior insular cortex and would be associated with an increase in choline concentration at this level. Clinical translation of these preclinical results is feasible in practice since choline concentration can be determined in the brain by non-invasive magnetic resonance spectroscopy.

Detailed Description

The objective of this study is to demonstrate a significant increase in choline concentration in the insular cortex of patients with an oxaliplatin induced neuropathy. Other objectives will assess the correlation between metabolite concentrations in the insular cortex and frequency / intensity of pain and neuropathic symptoms, cold and heat-induced pain and comorbidities (anxiety, pain, quality of life).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Neuropathy, Painful

Keywords

Neuropathy, Oxaliplatin, Insula, choline

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

42 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Oxaliplatin and neuropathic pain

Arm Type

Experimental

Arm Description

The objective of this study is to demonstrate a significant increase in choline concentration in the insular cortex of patients with an oxaliplatin induced neuropathy. Other objectives will assess the correlation between metabolite concentrations in the insular cortex and frequency / intensity of pain and neuropathic symptoms, cold and heat-induced pain and comorbidities (anxiety, pain, quality of life).

Arm Title

Oxaliplatin without neuropathic pain

Arm Type

Other

Arm Description

The objective of this study is to demonstrate a significant increase in choline concentration in the insular cortex of patients with an oxaliplatin induced neuropathy. Other objectives will assess the correlation between metabolite concentrations in the insular cortex and frequency / intensity of pain and neuropathic symptoms, cold and heat-induced pain and comorbidities (anxiety, pain, quality of life).

Intervention Type

Procedure

Intervention Name(s)

NMR Spectroscopy

Primary Outcome Measure Information:

Title

Choline concentration assessed by NMR spectroscopy in the posterior insula

Time Frame

1 month after chemotherapy end

Secondary Outcome Measure Information:

Title

Metabolite concentrations assessed by NMR spectroscopy in the posterior insula

Description

Metabolite (choline, myo-inositol, N-acétylaspartate, créatine, glutamate/glutamine, lactate and taurine)

Time Frame