D-cycloserine in the Management of Chronic Low Back Pain

• Sponsor: Thomas J. Schnitzer (Other)
• Overall Status: Completed
• CT.gov ID: NCT00125528
• Collaborator: (none)
• Enrollment: 41
• Location: 1
• Arms: 2
• Duration (Months): 28
• Patients Per Site Per Month: 1.5

Study Details

Study Description

Brief Summary

Pre-clinical studies in rats suggest that D-cycloserine (DCS) is effective in the management of chronic neuropathic pain. This pilot study will attempt to determine the effect of D-cycloserine in the treatment of chronic low back pain. Other aims of this study are to determine the safety of D-cycloserine in the treatment of chronic low back pain and to determine which pain measurement scales are best at measuring the efficacy of treatment.

Condition or Disease	Intervention/Treatment	Phase
Low Back Pain; Pain	Drug: D-cycloserine; Drug: placebo	Phase 2

Detailed Description

Human brain imaging studies indicate that the medial prefrontal cortex activity can predict more than 80% of the variance of chronic back pain intensity. Therefore, the investigators have hypothesized that modulation of brain activity at this site should result in analgesia. D-cycloserine has been shown to potentiate conditioned fear extinction. Based on this the investigators hypothesize that chronic neuropathic pain (back pain with radiculopathy) is partially mediated or potentiated by decreased ability to extinguish the pain memory, which the investigators hypothesize to be mediated through reward/aversion brain circuitry, and specifically through medial prefrontal cortex. They have tested this idea in pre-clinical studies and demonstrated that rats with neuropathic pain show analgesia over the long-term when treated with D-cycloserine. In humans with chronic back pain, the investigators hypothesize that D-cycloserine will enhance extinction of back pain which in turn should result in reduced emotional relevance of the pain, that is reduced suffering. It is quite possible that the overall intensity of the back pain will be unaffected, however, the associated suffering will be significantly attenuated.

This will be a double-blind, randomized, parallel group escalating dose study comparing D-cycloserine twice a day (bid) with placebo bid in patients with chronic low back pain. Subjects meeting inclusion criteria will continue baseline medications and be treated for 12 weeks with study drug: 50 mg bid DCS or matching placebo for the first 4 weeks, then 100mg bid DCS or matching placebo for 4 weeks and finally 200mg bid DCS or matching placebo for 4 weeks. Assessments of efficacy and safety will be undertaken every 2 weeks using standard, validated instruments to evaluate change in pain, function, quality of life and adverse events.

Study Design

• Study Type: Interventional
• Actual Enrollment: 41 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: D-Cycloserine in the Management of Chronic Low Back Pain: A Double-Blind, Randomized, Placebo-Controlled Pilot Study
• Study Start Date: Jul 1, 2012
• Actual Primary Completion Date: Apr 1, 2014
• Actual Study Completion Date: Nov 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 D-cycloserine 50mg bid/100mg bid/200 mg bid	Drug: D-cycloserine; D-cycloserine 50 mg bid; D-cycloserine 100 mg bid; D-cycloserine 200 mg bid
Placebo Comparator: 2 placebo	Drug: placebo; placebo bid

Outcome Measures

Primary Outcome Measures

1. Change in Numeric Rating Scale (NRS-11) [6 weeks]

   Change in NRS score after 6 weeks of treatment as compared to baseline. The numeric rating scale is an 11-point rating scale wherein participants rated their current lower back pain intensity on a scale from 0 to 10, with 0 meaning no pain and 10 being the worst pain possible. Thus, a larger negative number indicates positive change and a higher efficacy.

Secondary Outcome Measures

1. McGill Pain Questionnaire (MPQ) [6 weeks]

   Change in MPQ score after 6 weeks of treatment as compared to baseline. The MPQ score uses a Pain Rating Index from 0 to 20 where 0 is evidence of no pain and 20 indicates the highest pain possible. A lower score is also indicative of a lower quality of pain. Thus, a larger negative number indicates positive change and therefore higher efficacy.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Must have a history of low back pain for a minimum of 6 months with or without radiation of pain to leg or buttocks.

• Must be 18 years of age.

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

• Must be in generally stable health

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

• If female, must be post-menopausal for at least one year or practicing an accepted, highly effective method of contraception or abstinence and plan to continue either during the course of the study.

• Must be able and willing to read and understand instructions as well as questionnaires

• Must sign an informed consent document after complete explanation of the study documenting that they understand the purpose of the study, procedures to be undertaken, possible benefits, potential risks, and are willing to participate.

Exclusion Criteria:

• Low back pain associated with any systemic signs or symptoms, e.g., fever, chills.

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

• Involvement in litigation regarding their back pain or have a disability claim or are receiving workman's compensation or seeking either as a result of their low back pain

• Neurologic disorder, including history of seizures

• Major psychiatric disorder during the past 6 months

• Moderate or severe depression as determined by the Beck Depression Inventory or any active suicidal ideation

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

• Significant renal disease or severe renal insufficiency

• History of, or current, substance abuse/dependence including alcohol

• Significantly abnormal laboratory values

• Pregnant or lactating at any time during the course of the study

• Known sensitivity to D-cycloserine

• Currently taking any of the following medications: ethionamide, dilantin, isoniazid (INH), pyridoxine (vitamin B6)

• In the judgment of the investigator, unable or unwilling to follow the protocol and instructions

• Any change in medication for back pain in the last 30 days.

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

• Thomas J. Schnitzer

Investigators

• Principal Investigator: Thomas J Schnitzer, M.D., Ph.D., Northwestern University
• Principal Investigator: Vania Apkarian, Ph.D., Northwestern University

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: Thomas J. Schnitzer, professor, Northwestern University
• ClinicalTrials.gov Identifier: NCT00125528
• Other Study ID Numbers: A1159
• First Posted: Aug 1, 2005
• Last Update Posted: Feb 9, 2017
• Last Verified: Dec 1, 2016

• Keywords provided by Thomas J. Schnitzer, professor, Northwestern University: chronic pain; low back pain; D-cycloserine
• Additional relevant MeSH terms: Back Pain; Low Back Pain; Cycloserine

Study Results

Participant Flow

Arm/Group Title	D-cycloserine	Placebo
Arm/Group Description	D-cycloserine: D-cycloserine 50 mg bid; D-cycloserine 100 mg bid; D-cycloserine 200 mg bid	placebo: placebo bid
Period Title: Overall Study
STARTED	20	21
COMPLETED	18	20
NOT COMPLETED	2	1

Baseline Characteristics

Arm/Group Title	D-cycloserine	Placebo	Total
Arm/Group Description	D-cycloserine: D-cycloserine 50 mg bid; D-cycloserine 100 mg bid; D-cycloserine 200 mg bid	placebo: placebo bid	Total of all reporting groups
Overall Participants	20	21	41
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.65 (11.56)	54.76 (10.84)	54.71 (11.06)
Gender (Count of Participants)
Female	14 70%	11 52.4%	25 61%
Male	6 30%	10 47.6%	16 39%
Numeric Rating Scale (NRS-11) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	6.47 (1.40)	6.6 (1.50)	6.54 (1.45)

Outcome Measures

1. Primary Outcome

Title	Change in Numeric Rating Scale (NRS-11)
Description	Change in NRS score after 6 weeks of treatment as compared to baseline. The numeric rating scale is an 11-point rating scale wherein participants rated their current lower back pain intensity on a scale from 0 to 10, with 0 meaning no pain and 10 being the worst pain possible. Thus, a larger negative number indicates positive change and a higher efficacy.
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	D-cycloserine	Placebo
Arm/Group Description	D-cycloserine: D-cycloserine 50 mg bid; D-cycloserine 100 mg bid; D-cycloserine 200 mg bid	placebo: placebo bid
Measure Participants	18	20
Mean (Standard Deviation) [units on a scale]	-2.47 (0.50)	-1.55 (0.50)

2. Secondary Outcome

Title	McGill Pain Questionnaire (MPQ)
Description	Change in MPQ score after 6 weeks of treatment as compared to baseline. The MPQ score uses a Pain Rating Index from 0 to 20 where 0 is evidence of no pain and 20 indicates the highest pain possible. A lower score is also indicative of a lower quality of pain. Thus, a larger negative number indicates positive change and therefore higher efficacy.
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	D-cycloserine	Placebo
Arm/Group Description	D-cycloserine: D-cycloserine 50 mg bid; D-cycloserine 100 mg bid; D-cycloserine 200 mg bid	placebo: placebo bid
Measure Participants	18	20
Mean (Standard Deviation) [units on a scale]	-2.80 (0.66)	-1.00 (0.66)

Adverse Events

Arm/Group Title	D-cycloserine		Placebo
Arm/Group Description	D-cycloserine: D-cycloserine 50 mg bid; D-cycloserine 100 mg bid; D-cycloserine 200 mg bid		placebo: placebo bid
All Cause Mortality
	D-cycloserine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	D-cycloserine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/21 (0%)
Other (Not Including Serious) Adverse Events
	D-cycloserine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/20 (15%)		5/21 (23.8%)
General disorders
Headache	1/20 (5%)	1	3/21 (14.3%)	3
Nervous system disorders
Numbness/Tingling	3/20 (15%)	3	0/21 (0%)	0
Skin and subcutaneous tissue disorders
Lower Extremity Edema	0/20 (0%)	0	2/21 (9.5%)	2

Limitations/Caveats

It is not clear whether observed effects are due to escalating dose or duration of D-cycloserine use. A larger population and longer duration of treatment would be needed to determine this.

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.