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| ID | Type | Description | Link |
|---|---|---|---|
| A-20364 | Other Grant/Funding Number | Department of Defense |
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Insufficient funding to complete the study
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| Name | Class |
|---|---|
| United States Department of Defense | FED |
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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.
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. Magnetic resonance imaging (MRI), anatomical MRI, resting state functional MRI (fMRI), diffusion-tensor imaging (DTI) MRI, and arterial spin labeling (ASL) will be performed at baseline and at the end of 12 weeks for individuals completing MRI.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| D-cycloserine | Experimental | D-cycloserine 200 mg twice daily |
|
| Placebo | Placebo Comparator | Placebo twice daily |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| D-cycloserine | Drug | 200 mg twice daily |
| |
| Placebo |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Numeric Rating Scale (NRS) Pain Score 0-10; Higher Worse | 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. | 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Effect of Gender on Magnitude of Pain Response. | Assess the effect of gender on the on the pain rating response in each group (pain rating scale: 0 (no pain) to 10 (highest pain)). | 12 weeks |
| Brain Biomarkers (MRI) |
Not provided
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 patient reported outcomes (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
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:
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| Name | Affiliation | Role |
|---|---|---|
| Thomas J. Schnitzer, MD, PhD | Northwestern University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Northwestern University Feinberg School of Medicine | Chicago | Illinois | 60611 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35612403 | Derived | Pinto CB, Bielefeld J, Barroso J, Yip B, Huang L, Schnitzer T, Apkarian AV. Chronic pain domains and their relationship to personality, abilities, and brain networks. Pain. 2023 Jan 1;164(1):59-71. doi: 10.1097/j.pain.0000000000002657. Epub 2022 Apr 20. No abstract available. |
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There was an error in the study drug dispensation process that resulted in the incorrect treatment assignment being dispensed.
Adverse events are reported for all participants who were randomized (n=203) based on the treatment received (safety population). For the primary efficacy outcome results, only those participants who were enrolled up to the time of the error in allocation were included in those analyses (n=170).
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| ID | Title | Description |
|---|---|---|
| FG000 | D-cycloserine | D-cycloserine 200 mg twice daily |
| FG001 | Placebo | Placebo twice daily |
| FG002 | D-cycloserine (Secondary) | The participants in this group were incorrectly randomized to D-cycloserine. They were excluded from efficacy analyses, but were included in safety analyses. |
| FG003 | Placebo (Secondary) | The participants in this group were incorrectly randomized to Placebo. They were excluded from efficacy analyses, but were included in safety analyses. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | D-cycloserine | D-cycloserine 200 mg twice daily |
| BG001 | Placebo | Placebo twice daily |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Numeric Rating Scale (NRS) Pain Score 0-10; Higher Worse | 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. | The participants in the secondary sample were incorrectly randomized. They were excluded from efficacy analyses, but were included in safety analyses. | Posted | Mean | Standard Error | units on a scale | 12 weeks |
|
AEs were collected throughout the entire study period, starting on screening (visit 1) to week 24 (final visit).
Adverse events are reported for all participants who were randomized (n=203) based on the treatment received (safety population). For the primary efficacy outcome results, only those participants who were enrolled up to the time of the error in allocation were included in those analyses (n=170).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | D-cycloserine | D-cycloserine 200 mg twice daily | 0 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Stroke | Vascular disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Santiago Espinosa Salas | Northwestern University Feinberg School of Medicine | 312 503 3283 | santiagoespinosa@northwestern.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Apr 24, 2024 | Feb 14, 2025 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D017116 | Low Back Pain |
| D010146 | Pain |
| D059350 | Chronic Pain |
| ID | Term |
|---|---|
| D001416 | Back Pain |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D003523 | Cycloserine |
| ID | Term |
|---|---|
| D007555 | Isoxazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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Triple
| Drug |
twice daily |
|
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.
| 12 weeks |
| Patient Global Assessment | A 5-point scale used to reflect the global impact of pain from the patient's perspective. Scale range 0-10; higher = worse. | 12 weeks |
| Patient Global Impression of Change | 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. Scale range 1-7, higher = worse. | 12 weeks |
| McGill Pain Questionnaire (MPQ) | A 17-item self-reported measure assessing both the quality and intensity of subjective pain. Score 0-45, higher worse | 12 weeks |
| PainDETECT Questionnaire (PDQ) | A 14-item self-reported measure assessing qualities for pain of neuropathic origin to distinguish pain severity. Score 0-38; higher more neuropathic | 12 weeks |
| Beck Depression Inventory (BDI) | A 21-item self-report rating inventory that measures characteristic attitudes and symptoms of depression. Score 0-63, higher worse | 12 week |
| Positive and Negative Affect Schedule (PANAS) - Positive | A self-report questionnaire consisting of two 10-item (5-point) scales to measure both positive and negative affects of pain. Score 10-50; higher more positive | 12 weeks |
| Pain Catastrophizing Scale (PCS) | 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). Score 0-52, higher worse | 12 weeks |
| Multidimensional Assessment of Interoceptive Awareness (MAIA) | A 32-item self-reported measure delineating between beneficial versus maladaptive interoceptive attention. Score 0-160, higher more awareness. | 12 weeks |
| Oswestry Disability Index (ODI) | 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. Score 0-50; higher is greater disability | 12 weeks |
| 12-Item Short Form Survey (SF-12) - Mental | A 12-item self-report questionnaire measuring functional health and well-being from the patient's point of view. The SF-12 measures patient reported, health related quality of life from 0 to 100, with higher scores indicating better physical and mental health functioning. | 12 weeks |
| Positive and Negative Affect Schedule (PANAS) - Negative | A self-report questionnaire consisting of two 10-item (5-point) scales to measure both positive and negative affects of pain. Score 10-50; higher more positive | 12 weeks |
| 12-Item Short Form Survey (SF-12) - Physical | A 12-item self-report questionnaire measuring functional health and well-being from the patient's point of view. The SF-12 measures patient reported, health related quality of life from 0 to 100, with higher scores indicating better physical and mental health functioning. | 12 weeks |
| Lost to Follow-up |
|
| Adverse Event |
|
| Lack of Efficacy |
|
| Physician Decision |
|
| Study Terminated Early |
|
| BG002 |
| Total |
Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Pain Numeric Rating Scale (NRS) | Mean | Standard Deviation | units on a scale |
|
| painDETECT | Mean | Standard Deviation | units on a scale |
|
| Positive and Negative Affect Schedule (PANAS) Positive | Mean | Standard Deviation | units on a scale |
|
| Positive and Negative Affect Schedule (PANAS) Negative | Mean | Standard Deviation | units on a scale |
|
| Beck Depression Inventory (BDI) | Mean | Standard Deviation | units on a scale |
|
| Pain Catastrophizing Scale (PCS) | Mean | Standard Deviation | units on a scale |
|
| Oswestry Disability Index (ODI) | Mean | Standard Deviation | units on a scale |
|
| SF-12 Mental Health | Mean | Standard Deviation | units on a scale |
|
| SF-12 Physical Health | Mean | Standard Deviation | units on a scale |
|
| Patient Global Assessment (PGA) of Low Back Pain | Mean | Standard Deviation | units on a scale |
|
| OG002 |
| D-cycloserine (Secondary) |
The participants in this group were incorrectly randomized to D-cycloserine. They were excluded from efficacy analyses, but were included in safety analyses. |
| OG003 | Placebo (Secondary) | The participants in this group were incorrectly randomized to Placebo. They were excluded from efficacy analyses, but were included in safety analyses. |
|
|
| Secondary | Effect of Gender on Magnitude of Pain Response. | Assess the effect of gender on the on the pain rating response in each group (pain rating scale: 0 (no pain) to 10 (highest pain)). | The participants in the secondary sample were incorrectly randomized. They were excluded from efficacy analyses, but were included in safety analyses. | Posted | Mean | Standard Deviation | units on a scale | 12 weeks |
|
|
|
| Secondary | Brain Biomarkers (MRI) | 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. | Not Posted | Apr 2028 | 12 weeks | Participants |
| Secondary | Patient Global Assessment | A 5-point scale used to reflect the global impact of pain from the patient's perspective. Scale range 0-10; higher = worse. | The participants in the secondary sample were incorrectly randomized. They were excluded from efficacy analyses, but were included in safety analyses. | Posted | Mean | Standard Deviation | score on a scale | 12 weeks |
|
|
|
| Secondary | Patient Global Impression of Change | 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. Scale range 1-7, higher = worse. | The participants in the secondary sample were incorrectly randomized. They were excluded from efficacy analyses, but were included in safety analyses. | Posted | Mean | Standard Deviation | score on a scale | 12 weeks |
|
|
|
| Secondary | McGill Pain Questionnaire (MPQ) | A 17-item self-reported measure assessing both the quality and intensity of subjective pain. Score 0-45, higher worse | The participants in the secondary sample were incorrectly randomized. They were excluded from efficacy analyses, but were included in safety analyses. | Posted | Mean | Standard Deviation | score on a scale | 12 weeks |
|
|
|
| Secondary | PainDETECT Questionnaire (PDQ) | A 14-item self-reported measure assessing qualities for pain of neuropathic origin to distinguish pain severity. Score 0-38; higher more neuropathic | The participants in the secondary sample were incorrectly randomized. They were excluded from efficacy analyses, but were included in safety analyses. | Posted | Mean | Standard Deviation | score on a scale | 12 weeks |
|
|
|
| Secondary | Beck Depression Inventory (BDI) | A 21-item self-report rating inventory that measures characteristic attitudes and symptoms of depression. Score 0-63, higher worse | The participants in the secondary sample were incorrectly randomized. They were excluded from efficacy analyses, but were included in safety analyses. | Posted | Mean | Standard Deviation | score on a scale | 12 week |
|
|
|
| Secondary | Positive and Negative Affect Schedule (PANAS) - Positive | A self-report questionnaire consisting of two 10-item (5-point) scales to measure both positive and negative affects of pain. Score 10-50; higher more positive | The participants in the secondary sample were incorrectly randomized. They were excluded from efficacy analyses, but were included in safety analyses. | Posted | Mean | Standard Deviation | score on a scale | 12 weeks |
|
|
|
| Secondary | Pain Catastrophizing Scale (PCS) | 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). Score 0-52, higher worse | The participants in the secondary sample were incorrectly randomized. They were excluded from efficacy analyses, but were included in safety analyses. | Posted | Mean | Standard Deviation | score on a scale | 12 weeks |
|
|
|
| Secondary | Multidimensional Assessment of Interoceptive Awareness (MAIA) | A 32-item self-reported measure delineating between beneficial versus maladaptive interoceptive attention. Score 0-160, higher more awareness. | Not Posted | Apr 2028 | 12 weeks | Participants |
| Secondary | Oswestry Disability Index (ODI) | 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. Score 0-50; higher is greater disability | The participants in the secondary sample were incorrectly randomized. They were excluded from efficacy analyses, but were included in safety analyses. | Posted | Mean | Standard Deviation | score on a scale | 12 weeks |
|
|
|
| Secondary | 12-Item Short Form Survey (SF-12) - Mental | A 12-item self-report questionnaire measuring functional health and well-being from the patient's point of view. The SF-12 measures patient reported, health related quality of life from 0 to 100, with higher scores indicating better physical and mental health functioning. | The participants in the secondary sample were incorrectly randomized. They were excluded from efficacy analyses, but were included in safety analyses. | Posted | Mean | Standard Deviation | score on a scale | 12 weeks |
|
|
|
| Secondary | Positive and Negative Affect Schedule (PANAS) - Negative | A self-report questionnaire consisting of two 10-item (5-point) scales to measure both positive and negative affects of pain. Score 10-50; higher more positive | The participants in the secondary sample were incorrectly randomized. They were excluded from efficacy analyses, but were included in safety analyses. | Posted | Mean | Standard Deviation | score on a scale | 12 weeks |
|
|
|
| Secondary | 12-Item Short Form Survey (SF-12) - Physical | A 12-item self-report questionnaire measuring functional health and well-being from the patient's point of view. The SF-12 measures patient reported, health related quality of life from 0 to 100, with higher scores indicating better physical and mental health functioning. | The participants in the secondary sample were incorrectly randomized. They were excluded from efficacy analyses, but were included in safety analyses. | Posted | Mean | Standard Deviation | score on a scale | 12 weeks |
|
|
|
| 113 |
| 2 |
| 113 |
| 13 |
| 113 |
| EG001 | Placebo | Placebo twice daily | 0 | 90 | 4 | 90 | 10 | 90 |
| Severe COVID-19 Infection | Infections and infestations | Systematic Assessment |
|
| Severe Back Pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Total Knee Replacement | Surgical and medical procedures | Systematic Assessment |
|
| Upper Respiratory Infection | Infections and infestations | Systematic Assessment |
|
Not provided
Not provided
| D023303 |
| Oxazolidinones |
| D010080 | Oxazoles |
| D012694 | Serine |
| D021542 | Amino Acids, Neutral |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |