D-cycloserine for the Treatment of Chronic, Refractory Low Back Pain

Sponsor

Northwestern University (Other)

Overall Status

Recruiting

CT.gov ID

NCT03535688

Collaborator

United States Department of Defense (U.S. Fed)

244

Enrollment

Location

Arms

68.1

Anticipated Duration (Months)

3.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of D-cycloserine versus placebo in relieving the signs and symptoms of patients with chronic lower back pain.

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

Detailed Description

This is a 26-week, double-blind, randomized, placebo-controlled two-arm parallel-group trial of d-cycloserine, a pharmacological treatment selected based on positive results from previous preclinical and clinical studies, for the treatment of chronic, refractory low back pain (CBP). After a 2-week screening period, individuals will be randomized to receive either 12 weeks of d-cycloserine or placebo and then followed for an additional 12 weeks to evaluate persistence of benefit at study endpoint, 24 weeks after randomization. During the 12-week treatment period, participants will undergo evaluation at baseline and at clinic visits on weeks 2, 6 and 12 after randomization to assess pain, proper treatment use and side effects. During the subsequent 12-week follow-up period, pain and safety will continue to be assessed monthly by phone calls. All patients will also be assessed daily using an electronic diary (eDiary) to record pain and mood. T1-MRI, resting state fMRI DTI-MRI, and ASL will be performed at baseline and at the end of 12 weeks for individuals completing MRI.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

244 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Masking Description:

Triple

Primary Purpose:

Treatment

Official Title:

D-cycloserine for the Treatment of Chronic, Refractory Low Back Pain

Actual Study Start Date :

Mar 30, 2018

Anticipated Primary Completion Date :

Aug 1, 2023

Anticipated Study Completion Date :

Dec 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: D-cycloserine D-cycloserine 200 mg BID (twice daily)	Drug: D-cycloserine 200 mg BID (twice daily)
Placebo Comparator: Placebo Placebo BID (twice daily)	Drug: Placebo BID (twice daily)

Arm

Intervention/Treatment

Experimental: D-cycloserine

D-cycloserine 200 mg BID (twice daily)

Drug: D-cycloserine

200 mg BID (twice daily)

Placebo Comparator: Placebo

Placebo BID (twice daily)

Drug: Placebo

BID (twice daily)

Outcome Measures

Primary Outcome Measures

Change in Numeric Rating Scale (NRS) pain score [12 weeks]
Mean pain levels will be assessed at study baseline and compared to mean pain levels at Week 12 (study efficacy endpoint). Pain will be assessed using an 11-point NRS scale.

Secondary Outcome Measures

Gender (male/female) [12 weeks]
Assess the effect of gender on magnitude of pain response
Brain biomarkers (MRI) [12 weeks]
Evaluate interaction between the primary endpoint and specified brain biomarkers, with particular attention to corticostriatal connectivity. Whole-brain exploratory analyses will also be used to identify both brain predictors or treatment response and brain reorganization in response to treatment.
Patient Global Assessment [12 weeks]
A 5-point scale used to reflect the global impact of pain from the patient's perspective.
Patient Global Impression of Change [12 weeks]
A 7-point self-report measure that reflects a patient's belief about the efficacy of treatment by depicting a patient's rating of overall improvement.
McGill Pain Questionnaire (MPQ) [12 weeks]
A 17-item self-reported measure assessing both the quality and intensity of subjective pain.
painDETECT Questionnaire (PDQ) [12 weeks]
A 14-item self-reported measure assessing qualities for pain of neuropathic origin to distinguish pain severity.
Beck Depression Inventory (BDI) [12 week]
A 21-item self-report rating inventory that measures characteristic attitudes and symptoms of depression.
Positive and Negative Affect Schedule (PANAS) [12 weeks]
A self-report questionnaire consisting of two 10-item (5-point) scales to measure both positive and negative affects of pain.
Pain Catastrophizing Scale (PCS) [12 weeks]
A 13-item scale assessing the degree of catastrophic cognitions in the sensation of pain. The scale ranges from 1 (not at all) to 4 (always).
Multidimensional Assessment of Interoceptive Awareness (MAIA) [12 weeks]
A 32-item self-reported measure delineating between beneficial versus maladaptive interoceptive attention.
Oswestry Disability Index (ODI) [12 weeks]
A 10-item self-reported measure quantifying a subjective percentage score of level of function (disability) in activities of daily living in those with chronic low back pain.
SF-12 Health Survey [12 weeks]
A 12-item self-report questionnaire measuring functional health and well-being from the patient's point of view.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Must have a history of low back pain for a minimum of 6 months with or without signs and symptoms of radiculopathy
Male or female, age 18 years or older, (no racial/ethnic restrictions)
Must have an average pain score of ≥ 4 (on a 0-10 NRS) over a 5-7 day period (minimum of daily eDiary entries for at least 5 of 7 days) immediately preceding the baseline visit (visit 2)
Must be willing to read and able to understand instructions as well as PROs
Must be in generally stable health
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
Must be willing to discontinue all pain medications for chronic back pain (listed below) except the study medication and rescue medication provided and not use the following prohibited pain medications throughout the duration of the treatment period
analgesics including OTC medications
NSAIDS including OTC medications
Coxibs
Opioids
Muscle relaxants
Gabapentinoids including pregabalin and gabapentin
Must be willing to comply with recording pain, mood, and study treatment adherence twice daily using study eDiary
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 during the course of the study.

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, or history of surgery or tumor in the back within the past 6 months
Involvement in litigation regarding their back pain or has a disability claim or is receiving workman's compensation or is seeking either as a result of their low back pain
Epidural steroid injection within the past 3 months
History of seizures
Major new or untreated psychiatric disorder during the past 6 months and/or ongoing treatment with buproprion or fluphenazine
Beck Depression Inventory II score of >28
Significant renal disease or severe renal insufficiency
Substance abuse/dependence including alcohol within the past 6 months
Significantly abnormal laboratory values
Pregnant or lactating at the time of randomization
Known sensitivity to D-cycloserine
Currently taking any of the following medications: ethionamide, dilantin, isoniazid (INH)
In the judgment of the investigator, unable or unwilling to follow the protocol and instructions
Any change in medication or physical therapy regime for back pain in the last 30 days.
Chronic progressive neurologic conditions, including Parkinson's disease, Alzheimer's disease, and other conditions associated with dementia
Other medical disease such as clinically significant congestive heart failure, coronary or peripheral vascular disease, chronic obstructive lung disease, or malignancy
Presence of undiagnosed skin lesions or history of melanoma
Current use of recreational drugs
Current use of medical marijuana
High dose opioid prophylaxis, defined as > 50mg morphine equivalent/day
Intra-axial implants (e.g. spinal cord stimulators or pumps)
Pregnancy or inability to use an effective method of birth control in sexually active men and women while taking the study drug and for one week thereafter. Barrier contraceptives (condoms or diaphragm) with spermicide, intrauterine devices (IUD's), hormonal contraceptives, oral contraceptive pills, surgical sterilization, and complete abstinence are examples of effective methods of contraception.
Following laboratory abnormalities: liver function tests (SGOT/SGPT) greater than 2.5 times the upper limit of normal; unexplained anemia; evidence of renal insufficiency (creatinine > upper limit of normal) or any other abnormality that the principal investigator feels puts the participant at risk during the study.
Any medical condition that in the investigator's judgment may prevent the individual from completing the study or put the individual at undue risk
Lactose allergy
Ongoing participation in another clinical research study involving an investigational product or having received another investigational product within the last 90 days