Clinical Management of Neuropathic Pain With Ramelteon

• Sponsor: Massachusetts General Hospital (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00753623
• Collaborator: Takeda Pharmaceuticals North America, Inc. (Industry)
• Enrollment: 23
• Location: 1
• Arms: 2
• Duration (Months): 39
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Neuropathic Pain	Drug: Ramelteon; Drug: Placebo	N/A

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 Design

• Study Type: Interventional
• Actual Enrollment: 23 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Clinical Management of Neuropathic Pain With Ramelteon
• Study Start Date: Sep 1, 2008
• Actual Primary Completion Date: Dec 1, 2010
• Actual Study Completion Date: Dec 1, 2011

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. Difference in Visual Analog Scale (VAS) for Pain (0-10) Between Treatments [VAS score at baseline and after the treatment period]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114

Sponsors and Collaborators

• Massachusetts General Hospital
• Takeda Pharmaceuticals North America, Inc.

Investigators

• Principal Investigator: Jianren Mao, M.D., Ph. D., Massachusetts General Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jianren Mao, MD, PhD, Principal Investigator, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT00753623
• Other Study ID Numbers: 2008P-000988
• First Posted: Sep 16, 2008
• Last Update Posted: May 15, 2017
• Last Verified: Apr 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Jianren Mao, MD, PhD, Principal Investigator, Massachusetts General Hospital: Pain; Neuropathic pain; Pain scores
• Additional relevant MeSH terms: Neuralgia

Study Results

Participant Flow

Recruitment Details	Subjects were recruited in person at the MGH Center for Pain or by advertisement throughout MGH and the local community.

Arm/Group Title	Placebo Phase I; Ramelteon Phase II	Ramelton Phase I; Placebo Phase II
Arm/Group Description	In a crossover design, a subject was first assigned to the placebo and then switched over to the ramelteon. Ramelteon : ramelteon (8 mg)	In a crossover design, a subject was first assigned to the ramelteon and then switched over to the placebo. Ramelteon : ramelteon (8 mg)
Period Title: Phase I (14 Days)
STARTED	11	12
COMPLETED	9	8
NOT COMPLETED	2	4
Period Title: Phase I (14 Days)
STARTED	9	8
COMPLETED	8	8
NOT COMPLETED	1	0
Period Title: Phase I (14 Days)
STARTED	8	8
COMPLETED	8	7
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	Placebo Phase I; Ramelteon Phase II	Ramelton Phase I; Placebo Phase II	Total
Arm/Group Description	In a crossover design, a subject was first assigned to the placebo and then switched over to the ramelteon. Ramelteon : ramelteon (8 mg)	In a crossover design, a subject was first assigned to the ramelteon and then switched over to the placebo. Ramelteon : ramelteon (8 mg)	Total of all reporting groups
Overall Participants	11	12	23
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	11 100%	12 100%	23 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	7 63.6%	5 41.7%	12 52.2%
Male	4 36.4%	7 58.3%	11 47.8%
Region of Enrollment (Count of Participants)
United States	11 100%	12 100%	23 100%

Outcome Measures

1. Primary Outcome

Title	Difference in Visual Analog Scale (VAS) for Pain (0-10) Between Treatments
Description	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.
Time Frame	VAS score at baseline and after the treatment period

Outcome Measure Data

Analysis Population Description

Only 15 subjects completed both treatment phases so we only included these subjects in the analysis.

Arm/Group Title	Ramelteon	Placebo
Arm/Group Description	Participants who received Ramelteon 8 mg during the first or last 2 weeks of the study.	Participants who received placebo medication during the first or last 2 weeks of the study.
Measure Participants	15	15
Mean (Standard Deviation) [units on a scale]	-1.0 (1.4)	-1.1 (1.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramelteon, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	>0.05
	Comments
	Method	t-test, 2 sided
	Comments

Adverse Events

Time Frame	Two weeks for each intervention and a 1 week period of no intervention in between phases.
Arm/Group Title	Ramelteon		Placebo
Arm/Group Description	Participants who received Ramelteon 8 mg during the first or last 2 weeks of the study.		Participants who received placebo medication during the first or last 2 weeks of the study.
All Cause Mortality
	Ramelteon		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Ramelteon		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/23 (4.3%)		0/23 (0%)
Immune system disorders
Hospitalization	1/23 (4.3%)	1	0/23 (0%)	0
Other (Not Including Serious) Adverse Events
	Ramelteon		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/23 (0%)		0/23 (0%)

Limitations/Caveats

Problems with recruitment and termination of the study consequently resulted in uninterpretable data.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.