Sleep and Neuropathic Pain - Intervention Study on Pregabalin

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

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.

Study Overview

• Status: Recruiting
• Conditions: Sleep Disorder; Insomnia; Neuropathic Pain
• Intervention / Treatment: Drug: Pregabalin

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hanna Harno, PhD; Phone Number: +358503427375; Email: hanna.harno@hus.fi
• Study Contact Backup: Name: Eija Kalso, PhD; Phone Number: +358504270609; Email: eija.kalso@helsinki.fi

Study Locations

• Finland
  • HUS
    • Helsinki, HUS, Finland, 00029
      • Recruiting
      • Helsinki University Central Hospital
      • Contact: Hanna T Harno, MD, PhD; Phone Number: +358503427375; Email: hanna.harno@hus.fi
      • Principal Investigator: Eija Kalso, MD, PhD
      • Sub-Investigator: Miguel Munoz, MD, PhD
      • Sub-Investigator: Yevhen Hlushchuk, MD, PhD
  • Uusimaa
    • Helsinki, Uusimaa, Finland, 00029
      • Recruiting
      • Helsinki University Hospital, Department of Neurology
      • Contact: Hanna Harno, PhD; Phone Number: +358503427375; Email: hanna.harno@hus.fi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High ISI; Patients that have clinically significant insomnia according to ISI questionnaire (score 15 or more) at baseline.	Drug: Pregabalin; 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.; Other Names: Pregabalin for high insomnia patients with painful neuropathy; Pregabalin for low insomnia patients with painful neuropathy
Experimental: Low ISI; Patients with no clinically significant insomnia according to ISI questionnaire (score 14 or less) at baseline.	Drug: Pregabalin; 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.; Other Names: Pregabalin for high insomnia patients with painful neuropathy; Pregabalin for low insomnia patients with painful neuropathy

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Helsinki University Central Hospital
• Collaborators: University of Helsinki
• Investigators: Study Chair: Hanna Harno, PhD, Helsinki University Hospital, Department of Neurology

Study record dates

Study Major Dates

• Study Start (Actual): November 22, 2022
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: May 29, 2023
• First Submitted That Met QC Criteria: November 24, 2023
• First Posted (Estimated): December 5, 2023

Study Record Updates

• Last Update Posted (Estimated): December 5, 2023
• Last Update Submitted That Met QC Criteria: November 24, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: polysomnography; fMRI; pregabalin; neuropathic pain; actigraphy
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Pain; Neurologic Manifestations; Neuromuscular Diseases; Peripheral Nervous System Diseases; Sleep Wake Disorders; Neuralgia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Anti-Anxiety Agents; Anticonvulsants; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Pregabalin
• Other Study ID Numbers: TYH2020214

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No