Sleep and Neuropathic Pain - Intervention Study on Pregabalin

Study Overview
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Brief Summary
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The goal of this clinical study is to study sleep and its microstructure in neuropathic pain patients who have or who do not have a clinically significant sleep disturbance, before and during (after 1-month stabile dosage) pregabalin treatment. To find out whether reduced pain by pregabalin associates with improved sleep quality; to study, using resting state fMRI, brain network connectivity and the volume of the choroid plexus before and during pregabalin treatment (after dosage stable for one month) at baseline and during stabile treatment with pregabalin, and to compare the usability and reliability of sleep-related information collected with sleep diaries, actigraphy, iButtons, and ambulatory polysomnography in peripheral painful neuropathy patients. The main questions it aims to answer are: Is pregabalin more efficacious in neuropathic pain patients who suffer from insomnia compared to those with no clinically meaningful sleep disturbance? Does sleep disturbance due to pain associate with brain network connectivity and may these changes be reversed by pregabalin treatment? Participants will Fulfill e-questionnaires and keep sleep diary before and after 1month stabile pregabalin intervention Before and after 1-month stabile pregabalin medication: 1-week Actiwatch monitoring, iButton (1 day and night), ambulatory polysomnography (1 night), brain fMRI. Researchers will compare patients with high ISI score patients to see if they benefit more from pregabalin treatment than those with low ISI score.

Detailed Description
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This is a clinical study to analyze sleep and pain and their response to pregabalin in 40 patients aged 18 to 75 years with chronic (duration>3 months) moderate to severe pain (NRS ≥ 4/10) due to peripheral neuropathy. The investigators divide patients to two groups according to scores in ISI: the ones with clinically significant insomnia with score 15 or more (ISI High) and the ones without marked insomnia with score 14 or lower (ISI Low). Sleep will be assessed by a sleep diary, iButton, polysomnography and 1-week Actiwatch monitoring before and after 1-month stabile pregabalin dosage. Additionally, at these time points, several questionnaires regarding pain, sleep, mood, and quality of life and functional brain MRI will be performed. At pregabalin administration, the dose is added three to four day intervals, if tolerated by the patient. After a maximum tolerated dose has been stable for 1 month, the sleep studies, questionnaires, and brain fMRI are repeated. The study duration is about 3 months.

Official Title
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Sleep Structure in Neuropathic Pain Patients, Psychological Factors, Brain Connectivity, and the Effect of Pregabalin on Sleep and Pain

Conditions
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Neuropathic Pain, Insomnia, Sleep Disorder

Intervention / Treatment
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* Drug: Pregabalin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chronic (duration > 3 months) painful peripheral neuropathy Pain moderate to severe (NRS ≥ 4/10) during the past week Exclusion Criteria: psychotic depression, clinically significant bipolar disorder contraindication for performing brain fMRI (metal in the body etc)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients start with pregabalin at dose 25mg-75mg per day according to their preference and dose will be added by 25mg to 75 mg/ 4 days up to the highest dosage the patient tolerates (maximum 300mg twice daily). After having pregabalin stabile for one month with the highest tolerated dosage, post-examinations are repeated while still using pregabalin.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High ISI<br>Patients that have clinically significant insomnia according to ISI questionnaire (score 15 or more) at baseline. | Drug: Pregabalin<br>* Pregabalin administration and titration to the highest dosage that the patient tolerates. The patient continues with the highest dose for one month and the pre-intervention studies are repeated.<br>* Other names: Pregabalin for low insomnia patients with painful neuropathy;|
| Experimental: Low ISI<br>Patients with no clinically significant insomnia according to ISI questionnaire (score 14 or less) at baseline. | Drug: Pregabalin<br>* Pregabalin administration and titration to the highest dosage that the patient tolerates. The patient continues with the highest dose for one month and the pre-intervention studies are repeated.<br>* Other names: Pregabalin for low insomnia patients with painful neuropathy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pregabalin response to pain | Pain intensity and interference assessed by numeric rating scale | Change from baseline pain intensity and interference immediately after the intervention | 
| Pregabalin effect on sleep stages | 1-night Ambulatory Polysomnography (NREM stage III) | Change from baseline immediately after the intervention | 
| Sleep disturbance associations to brain network connectivity | Brain fMRI for brain network connectivity | Change from baseline immediately after the intervention | 
| Sleep disturbance associations to choroid plexus volume in brain fMRI | Brain fMRI for choroid plexus volume measures | Change from baseline immediately after the intervention | 
| Pregabalin effect on circadian rhythms | 1-week actigraphy | Change from baseline immediately after the intervention | 
| Pregabalin effect on body temperature during sleep | 1-night body temperature measurement by iButton | Change from baseline immediately after the intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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polysomnography, actigraphy, fMRI, pregabalin, neuropathic pain