Effect of Milnacipran in Chronic Neuropathic Low Back Pain

• Sponsor: Northwestern University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01225068
• Collaborator: Forest Laboratories (Industry), Shirley Ryan AbilityLab (Other), Best Practice (Other)
• Enrollment: 40
• Location: 1
• Arms: 2
• Duration (Months): 18
• Patients Per Site Per Month: 2.2

Study Details

Study Description

Brief Summary

Low back pain is a public health problem affecting between 70-85% of adults at some time in their life. This study is being done to study the safety and effectiveness of the drug Milnacipran in treating chronic low back pain.

Condition or Disease	Intervention/Treatment	Phase
Low Back Pain	Drug: Milnacipran; Drug: Placebo	Phase 2

Detailed Description

This exploratory study aims to evaluate Milnacipran in individuals with chronic neuropathic low back pain. A sample of 40 individuals with chronic low back pain will be enrolled in a double-blind, randomized, parallel group study comparing twice daily administration of milnacipran with placebo (total 100 mg bid-or equivalent placebo dosing). The study will last 6 weeks with subjects being evaluated at the start of the study, at the end of a one-week drug-free period, and at 1, 2 and 6 weeks of treatment. Additionally, subjects will evaluated after treatment has ended. Both standard endpoint outcome measures as well as validated daily self-report measures of pain and activity/disability will be utilized.

Study Design

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: An Exploratory Randomized Placebo Controlled Trial of Milnacipran in Patients With Chronic Neuropathic Low Back Pain
• Study Start Date: Oct 1, 2010
• Actual Primary Completion Date: Jan 1, 2012
• Actual Study Completion Date: Apr 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Milnacipran milnacipran 50 mg bid; can be increased to 100 mg bid	Drug: Milnacipran; Total of 100 mg (50 mg twice a day) for 6 weeks. Option to increase to 200 mg (100 mg twice a day) after two weeks of treatment. Includes gradual escalation and discontinuation for week 1 and after week 6.; Other Names: Savella
Placebo Comparator: Placebo Placebo	Drug: Placebo; 2 matching pills per day for 6 weeks. Option to increase dose after two weeks of treatment. Includes gradual escalation and discontinuation for week 1 and after week 6.

Outcome Measures

Primary Outcome Measures

1. Effect Size of VAS Pain [6 weeks from baseline]

   Effect size (ES) calculation for VAS pain between milnacipran and placebo groups' ES is dimensionless; Visual analogue scale (VAS) measured pain in integral units from 0 (low end) to 100 (high end); ES (Cohen's d) is a well described statistical construct and is calculated from the difference between the means (determined at baseline and 6 weeks here) divided by the pooled standard deviation. This is the primary outcome measure.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. History of low back pain for a minimum of 6 months with radiation to leg or buttocks

2. Over 18 years of age and under 70

3. Must have a visual analogue scale (VAS) pain score >50mm

4. Must be in generally stable health

5. Must be willing to abstain from alcohol during the course of the study

6. If female, must be post-menopausal, or practicing a highly effective method of contraception or abstinence during the course of the study

7. Must be able to read and understand instructions and the questionnaires

8. Must be willing to participate in daily data collection requirements via telephone (IVRS)

9. Must understand all aspects of the study, and willing to sign an informed consent form in that regard.

Exclusion Criteria:

1. Low back pain associated with systemic signs or symptoms (e.g. fever or chills)

2. Evidence of rheumatoid arthritis, ankylosing spondylitis, acute vertebral fractures, fibromyalgia, history of surgery or tumor in the back

3. Involvement in litigation regarding back pain or other disability claim, or receiving workmen's compensation, or seeking either as a result of low back pain.

4. Neurological disorder including history of seizures

5. Major psychiatric disorder during the past six months

6. Active suicidal ideation or recent suicidal behavior

7. Significant other medical disease such as unstable diabetes mellitus, congestive heart failure, coronary or peripheral vascular disease, chronic obstructive lung disease or malignancy

8. Significant renal disease or severe renal insufficiency

9. History of, or current, substance abuse/dependence

10. Significantly abnormal laboratory values

11. Pregnant or lactating any time during the course of the study

12. Known sensitivity to Savella or other SNRI

13. Glaucoma

14. Taking any MAOI, sibutramine, digoxin, tricyclic antidepressants, other SNRI, Opioids.

15. Beck Depression Inventory Score >30

16. Current Sleep Disorder

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Northwestern University Feinberg School of Medicine	Chicago	Illinois	United States	60611

Sponsors and Collaborators

• Northwestern University
• Forest Laboratories
• Shirley Ryan AbilityLab
• Best Practice

Investigators

• Principal Investigator: Thomas J Schnitzer, MD, PhD, Northwestern University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Thomas J. Schnitzer, professor, Northwestern University
• ClinicalTrials.gov Identifier: NCT01225068
• Other Study ID Numbers: STU00036897
• First Posted: Oct 20, 2010
• Last Update Posted: Jan 17, 2014
• Last Verified: Dec 1, 2013

• Additional relevant MeSH terms: Back Pain; Low Back Pain; Milnacipran; Levomilnacipran

Study Results

Participant Flow

Recruitment Details	Outpatient clinic
Pre-assignment Detail	Screening visit prior to randomization

Arm/Group Title	Milnacipran	Placebo
Arm/Group Description	Milnacipran : Total of 100 mg (50 mg twice a day) for 6 weeks. Option to increase to 200 mg (100 mg twice a day) after two weeks of treatment. Includes gradual escalation and discontinuation for week 1 and after week 6.	Placebo treatment group
Period Title: Overall Study
STARTED	20	20
COMPLETED	16	19
NOT COMPLETED	4	1

Baseline Characteristics

Arm/Group Title	Milnacipran	Placebo	Total
Arm/Group Description	Milnacipran : Total of 100 mg (50 mg twice a day) for 6 weeks. Option to increase to 200 mg (100 mg twice a day) after two weeks of treatment. Includes gradual escalation and discontinuation for week 1 and after week 6.	Placebo treatment group	Total of all reporting groups
Overall Participants	20	20	40
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	20 100%	20 100%	40 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	47.1 (11.6)	48.3 (9.1)	47.7 (10.3)
Sex: Female, Male (Count of Participants)
Female	10 50%	11 55%	21 52.5%
Male	10 50%	9 45%	19 47.5%
Region of Enrollment (participants) [Number]
United States	20 100%	20 100%	40 100%

Outcome Measures

1. Primary Outcome

Title	Effect Size of VAS Pain
Description	Effect size (ES) calculation for VAS pain between milnacipran and placebo groups' ES is dimensionless; Visual analogue scale (VAS) measured pain in integral units from 0 (low end) to 100 (high end); ES (Cohen's d) is a well described statistical construct and is calculated from the difference between the means (determined at baseline and 6 weeks here) divided by the pooled standard deviation. This is the primary outcome measure.
Time Frame	6 weeks from baseline

Outcome Measure Data

Analysis Population Description

per protocol

Arm/Group Title	Placebo	Milnacipran
Arm/Group Description	Placebo arm	Milnacipran : Total of 100 mg (50 mg twice a day) for 6 weeks. Option to increase to 200 mg (100 mg twice a day) after two weeks of treatment. Includes gradual escalation and discontinuation for week 1 and after week 6.
Measure Participants	19	16
Mean (Standard Deviation) [units on a scale]	24.8 (32.5)	31.3 (26.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Milnacipran
	Comments	effect size is endpoint and not comparison
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	effect size
	Estimated Value	0.22
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	baseline to 8 weeks after randomization
Arm/Group Title	Milnacipran		Placebo
Arm/Group Description	Milnacipran : Total of 100 mg (50 mg twice a day) for 6 weeks. Option to increase to 200 mg (100 mg twice a day) after two weeks of treatment. Includes gradual escalation and discontinuation for week 1 and after week 6.		Placebo treatment group
All Cause Mortality
	Milnacipran		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Milnacipran		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		1/20 (5%)
Gastrointestinal disorders
colon resection	0/20 (0%)	0	1/20 (5%)	1
Other (Not Including Serious) Adverse Events
	Milnacipran		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/20 (70%)		10/20 (50%)
Gastrointestinal disorders
nausea	5/20 (25%)	5	1/20 (5%)	1
constipation	1/20 (5%)	1	2/20 (10%)	2
abdominal pain	1/20 (5%)	1	0/20 (0%)	0
dry mouth	3/20 (15%)	3	0/20 (0%)	0
General disorders
headache	2/20 (10%)	2	7/20 (35%)	7
drowsiness	1/20 (5%)	1	1/20 (5%)	1
fatigue	1/20 (5%)	1	0/20 (0%)	0
insomnia	0/20 (0%)	0	1/20 (5%)	1
Musculoskeletal and connective tissue disorders
knee pain	0/20 (0%)	0	1/20 (5%)	1
Nervous system disorders
dizziness	0/20 (0%)	0	3/20 (15%)	3
Renal and urinary disorders
urinary frequency	1/20 (5%)	1	0/20 (0%)	0
Reproductive system and breast disorders
sexual dysfunction	1/20 (5%)	1	1/20 (5%)	1
Skin and subcutaneous tissue disorders
itching	0/20 (0%)	0	1/20 (5%)	1

Limitations/Caveats

[Not Specified]

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.