Clinical Management of Neuropathic Pain With Ramelteon

This proposal is to conduct a double-blinded, randomized, placebo-controlled, crossover clinical study to examine the hypothesis that ramelteon would reduce pain score and improve functional status in subjects with neuropathic pain.

Study Overview

• Status: Terminated
• Conditions: Neuropathic Pain
• Intervention / Treatment: Drug: Ramelteon; Drug: Placebo

Detailed Description

Neuropathic pain is a chronic pain condition resulting from injury to the peripheral and/or central nervous system. Despite extensive research over the last several decades, neuropathic pain remains poorly managed due to the lack of effective pharmacological tools. To date, little has been known regarding the effect of melatonin and its analogues on clinical neuropathic pain. We propose to conduct a randomized, placebo-controlled, double-blinded, and crossover clinical trial to examine the effect of ramelteon [a melatonin (MT) 1/ MT2 receptor agonist] on neuropathic pain. We hypothesize that ramelteon would reduce pain score and improve functional status in subjects with neuropathic pain.

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subject will be between ages 18 to 65 years.
2. Subject has not been on ramelteon for at least one month.
3. Subject agrees to make no change in his/her current pain medications during the entire study period (5 weeks). This requirement will ensure that valid comparisons of primary and secondary measures can be made before and after the study.
4. Subject has a VAS pain score of 5 or above at the beginning of the study.
5. Subject has had a neuropathic pain condition as listed above for at least three months. This requirement is to avoid clinical uncertainty from an unstable pain condition and to minimize the study variation.
6. Female subjects of childbearing potential must have a negative urine pregnancy test at the initial visit.

Exclusion Criteria:

1. Subject has moderate to severe liver impairment.
2. Subject has Liver Function Tests (LFT's) >1.5X normal.
3. Subject has a history of renal impairment.
4. Subject has moderate or severe cardiac or pulmonary disease including a base line oxygen saturation of less than 95% on room air or any requirement for supplemental oxygen.
5. Subject has a history of glaucoma.
6. Subject has obstructive sleep apnea.
7. Subject is taking medications for sleep disorders including insomnia.
8. Subject has a major psychiatric disorder (major depression requiring a recent hospitalization within three months prior to the study; bipolar disorder; schizophrenia; psychotic disorders; substance abuse).
9. Subject has a history of dementia or delirium.
10. Subject has a history of falls.
11. Subject is pregnant or lactating.
12. Subject is using an illicit drug detected by a screening test.
13. Subject is currently taking Fluvoxamine.
14. Subject has been taking Ketoconazole in the past two weeks.
15. Subject has known hypersensitivity to ramelteon.
16. Subject has pending litigation related to his/her neuropathic pain condition.
17. Subject has Concurrent participation in other research drug trials or other study participation within 30 days of enrollment in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Ramelteon first, placebo second; In a crossover design, a subject will be first assigned to the ramelteon arm and then switched over to the placebo arm. As this is a double-blind study, neither the subject nor the study staff will know which intervention the subject is randomly assigned. The ramelteon dose is 8mg once a night.The ramelteon and placebo will be blinded by the central pharmacy. The subject is randomly assigned to first receive either ramelteon or placebo. The first intervention will be 14 days long. There is a 7 day washout period, and then the subject is assigned to the opposite intervention. The second intervention will be 14 days long.	Drug: Ramelteon; ramelteon (8 mg); Other Names: Rozerem; Drug: Placebo; In a crossover design, a subject will be first assigned to the ramelteon or placebo arm and then switched over to the opposite arm.
Placebo Comparator: Placebo first, ramelteon second; In a crossover design, a subject will be first assigned to the placebo arm and then switched over to the ramelteon arm. As this is a double-blind study, neither the subject nor the study staff will know which intervention the subject is randomly assigned. The ramelteon dose is 8mg once a night. The ramelteon and placebo will be blinded by the central pharmacy. The subject is randomly assigned to first receive either ramelteon or placebo. The first intervention will be 14 days long. There is a 7 day washout period, and then the subject is assigned to the opposite intervention. The second intervention will be 14 days long.	Drug: Ramelteon; ramelteon (8 mg); Other Names: Rozerem; Drug: Placebo; In a crossover design, a subject will be first assigned to the ramelteon or placebo arm and then switched over to the opposite arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in Visual Analog Scale (VAS) for Pain (0-10) Between Treatments	Subjects were asked to rate their pain the VAS with 0 being no pain and 10 being the worst pain they can imagine. The VAS scores were compared between the baseline and after a period of treatment. A negative number indicates an improvement in pain from baseline score.	VAS score at baseline and after the treatment period

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: Takeda Pharmaceuticals North America, Inc.
• Investigators: Principal Investigator: Jianren Mao, M.D., Ph. D., Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (Actual): December 1, 2010
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: September 15, 2008
• First Submitted That Met QC Criteria: September 15, 2008
• First Posted (Estimate): September 16, 2008

Study Record Updates

• Last Update Posted (Actual): May 15, 2017
• Last Update Submitted That Met QC Criteria: April 3, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: Pain; Neuropathic pain; Pain scores
• Additional Relevant MeSH Terms: Nervous System Diseases; Pain; Neurologic Manifestations; Neuromuscular Diseases; Peripheral Nervous System Diseases; Neuralgia
• Other Study ID Numbers: 2008P-000988

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No