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

Neuropathy Clinical Trial

— INSULOX  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02340403
• Other study ID #: CHU-0217
• Secondary ID: 2013-A01588-37
• Status: Completed
• Phase: N/A
• Start date: March 9, 2014
• Est. completion date: August 27, 2021

Study information

• Verified date: December 2021
• Source: University Hospital, Clermont-Ferrand
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: August 27, 2021
• Est. primary completion date: February 4, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Neuralgia
• Neuropathy
• Painful

Intervention

Procedure:
• NMR Spectroscopy

Locations

Country	Name	City	State
France	CHU de Clermont-Ferrand	Clermont-Ferrand

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Clermont-Ferrand

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Choline concentration assessed by NMR spectroscopy in the posterior insula		1 month after chemotherapy end
Secondary	Metabolite concentrations assessed by NMR spectroscopy in the posterior insula	Metabolite (choline, myo-inositol, N-acétylaspartate, créatine, glutamate/glutamine, lactate and taurine)	1 month and 6 months after chemotherapy end
Secondary	Pain intensity (VAS and BPI questionnaire)	(VAS and BPI questionnaire)	1 month and 6 months after chemotherapy end
Secondary	Neuropathic pain diagnostic 9DN4 interview questionnaire)		1 month and 6 months after chemotherapy end
Secondary	Neuropathic pain intensity (NPSI questionnaire)	NPSI questionnaire	1 month and 6 months after chemotherapy end
Secondary	BPI questionnaire		1 month and 6 months after chemotherapy end
Secondary	Quantitative sensory threshold (cold, heat, vibration)		1 month and 6 months after chemotherapy end
Secondary	Neuropathy grade		1 month and 6 months after chemotherapy end
Secondary	Anxiety and depression symptoms (HADS questionnaire)	HADS questionnaire	1 month and 6 months after chemotherapy end
Secondary	Intensity of chemotherapy-induced peripheral neuropathy (CIPN20 questionnaire)	CIPN20 questionnaire	1 month and 6 months after chemotherapy end
Secondary	Health related quality of life (QLQ-C30 questionnaire)	(QLQ-C30 questionnaire	at 1 month and 6 months after chemotherapy end