Neurosteroids as Novel Therapeutic Agents for Chronic Pain in OEF/OIF Veterans

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT01898013
Recruitment Status : Recruiting
First Posted : July 12, 2013
Last Update Posted : April 21, 2017
Information provided by (Responsible Party):
Durham VA Medical Center

Brief Summary:
The study design is a randomized, double-blind, two-arm trial of pregnenolone and placebo to determine the possible analgesic effects in OEF/OIF Veterans with chronic low back pain. The total study duration is 6 weeks (followed by two-follow up phone calls). All patients will monitor pain symptoms for one week with pain diaries, followed by a 1-week placebo-only lead-in period, 90 subjects will be randomly assigned to one of two groups. Of these subjects, 45 subjects will receive pregnenolone, and 45 subjects will receive placebo for 4 weeks. Patient interview assessments and laboratory studies will be performed at each interview time point. Pregnenolone, allopregnanolone and other neurosteroid metabolites will be determined by gas chromatography / mass spectrometry (GC/MS), proceeded by high performance liquid chromatography (HPLC).

Condition or disease Intervention/treatment Phase
Lower Back Pain Drug: Pregnenolone Drug: Placebo Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Neurosteroids as Novel Therapeutic Agents for Chronic Pain in OEF/OIF Veterans
Study Start Date : September 2013
Estimated Primary Completion Date : July 2017
Estimated Study Completion Date : July 2018

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Active Comparator: Pregnenolone

Pregnenolone fixed escalating up to 500mg/day will consist of the following schedule:

Visit 1 (week -1, screening visit) and pain symptom assessment (no study medication) Visit 2 (week 0) placebo lead-in (all participants) Visit 3 (week 1, baseline visit): 50mg PO, BID x 1 week, Visit 4 (week 2): 150mg PO, BID x 1 week, Visit 5 (week 3): 250mg PO, BID for two weeks. Visit 6 (week 5): No medication will be dispensed; study medication will be tapered by 100mg per day and then discontinued.

Drug: Pregnenolone
Placebo Comparator: Placebo

Placebo will be administered exactly the same as the active comparator (pregnenolone) and will consist of the following schedule:

Visit 1 (week -1, screening visit) and pain symptom assessment (no study medication) Visit 2 (week 0) placebo lead-in (all participants) Visit 3 (week 1, baseline visit): placebo PO, BID x 1 week, Visit 4 (week 2): placebo PO, BID x 1 week, Visit 5 (week 3): placebo PO, BID for two weeks. Visit 6 (week 5): No medication will be dispensed; study medication will be tapered in the exact manner as active study medication and then discontinued.

Drug: Placebo

Primary Outcome Measures :
  1. Pain rating [ Time Frame: an average of 7 weeks ]
    Primary efficacy outcome measure will be the weekly mean of the 24-hour average pain severity scores recorded daily on an 11-point Likert scale, an ordinal scale ranging from 0 (no pain) to 10 (worst pain).

Secondary Outcome Measures :
  1. Brief Pain Inventory [ Time Frame: an average of 7 weeks ]
    The The Brief Pain Inventory (BPI) is a self-reported scale that measures the severity of pain and the interference of pain on function. The scores range from 0 (no pain) to 10 (pain as severe as you can imagine). There are 4 questions assessing worst pain, least pain, average pain in the past 24 hours, and the pain right now. The Interference scores range from 0 (does not interfere) to 10 (completely interferes). There are 7 questions assessing the interference of pain in the past 24 hours for general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life.

  2. Beck Depression Inventory [ Time Frame: an average of 7 weeks ]
    The Beck Depression Inventory is a 21-item, self-report rating inventory that measures characteristic attitudes and symptoms of depression (Beck, et al., 1961). Scores range from 0 (no depression) to 63 (severe depression).

  3. Davidson Trauma Scale [ Time Frame: an average of 7 weeks ]
    The Davidson Trauma Scale (DTS) is a 17-item self-report measure that assesses the 17 DSM-IV symptoms of PTSD. Items are rated on 5-point frequency (0 = "not at all" to 4 = "every day") and severity scales (0 = "not at all distressing" to 4 = "extremely distressing"). Respondents are asked to identify the trauma that is most disturbing to them and to rate, in the past week, how much trouble they have had with each symptom. The DTS yields a frequency score (ranging from 0 to 68), severity score (ranging from 0 to 68), and total score (ranging from 0 to 136).

  4. Athens Insomnia Scale [ Time Frame: an average of 7 weeks ]
    The scale assesses the severity of insomnia using diagnostic criteria set forth by the International Classification of Diseases (ICD-10). The eight-item questionnaire evaluates sleep onset, night and early-morning waking, sleep time, sleep quality, frequency and duration of complaints, distress caused by the experience of insomnia, and interference with daily functioning. Scores range from 0 (no sleep disturbance) to 24 (significant sleep disturbance).

  5. The RAND 36-Item Health Survey [ Time Frame: an average of 7 weeks ]
    The RAND 36-Item Health Survey laps eight concepts: physical functioning, bodily pain, role limitations due to physical health problems, role limitations due to personal or emotional problems, emotional well-being, social functioning, energy/fatigue, and general health perceptions. It also includes a single item that provides an indication of perceived change in health. All items are scored so that a high score defines a more favourable health state. In addition, each item is scored on a 0 to 100 range so that the lowest and highest possible scores are set at 0 and 100, respectively. Scores represent the percentage of total possible score achieved. In step 2, items in the same scale are averaged together to create the 8 scale scores.

  6. Connor-Davidson Resilience Scale [ Time Frame: an average of 7 weeks ]
    The Connor-Davidson Resilience Scale (CD-RISC) has been developed and tested as (i) a measure of degree of resilience, (ii) as a predictor of outcome to treatment with medication or psychotherapy, stress management and resilience-building; (iii) as a marker of progress during treatment; (iv) as a marker of biological (i.e. physical) changes in the brain. The scale also has promise as a method to screen people for high, intermediate or low resilience. The CD-RISC comprises of 25 items, each rated on a 5-point scale (0-4), with higher scores reflecting greater resilience.

  7. Roland Morris Disability Questionnaire [ Time Frame: an average of 7 weeks ]
    The measure designed is to assess self-rated physical disability caused by low back pain. This is a 24-item questionnaire. The patient is asked to tick a statement when it applies to him that specific day, this makes it possible to follow changes in time. The end score is the sum of the ticked boxes. The score ranges from 0 (no disability) to 24 (max. disability).

  8. Patient's Global Impression of Change Scale [ Time Frame: an average of 7 weeks ]
    A self-report measure that reflects a patient's belief about the efficacy of treatment. There is a 10-point scale depicting patients rating of overall improvement and a 7-point scale to assess change in activity limitations, symptoms, emotions and overall quality of life. Higher scores are indicative of greater improvement for both scales.

  9. Digit Sequencing Task [ Time Frame: an average of 7 weeks ]

    Patients will be presented auditorily with clusters of numbers (e.g., 936) of increasing length. They are asked to tell the experimenter the numbers in order, from lowest to highest.

    Measures: number of correct responses

  10. Tower of London [ Time Frame: an average of 7 weeks ]

    Participants will look at two pictures simultaneously. Each picture will show three different colored balls arranged on three pegs, but the balls will be in a unique arrangement in each picture. The patient will give the minimum number of times the balls in one picture would have to be moved in order to make the arrangement of balls identical to that of the other, opposing picture.

    Measures: number of correct responses. 20 items administered. 22 items administered if items 1-2 are answered correctly. Scoring is 0-22 (0 being lowest score-greater impairment, 22 being highest score, no impairment).

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. OEF/OIF Veterans, 18-65 years of age, with chronic low back pain.
  2. Based on medical history and medical records, have low back pain (Thoracic Vertebrae 6 or below) present on most days for the preceding 6 months or longer, and fulfill all disease diagnostic criteria (please see disease diagnostic criteria below).
  3. Have a weekly mean of 24-hour average pain score ≥ 4 at baseline.
  4. Negative pregnancy test if female. Sexually active subjects are required to use a medically acceptable form of birth control if they are of childbearing potential and could become pregnant during the study. A medically acceptable form of birth control includes non-hormonal intrauterine devices, surgical sterilization, or double barrier methods (e.g., diaphragm with contraceptive jelly, condom with contraceptive foam, cervical caps with contraceptive jelly). Sexual abstinence with agreement to continue abstinence or to use a medically acceptable method of contraception (as listed above) should sexual activity occur is permissible.
  5. No change in medications less than 4 weeks before baseline.
  6. No anticipated need to alter psychotropic or pain medications for the 6-wk study duration (as determined by study physician's review of records and/or discussion with prescribing physician).
  7. Ability to fully participate in the informed consent process.

Exclusion Criteria:

  1. Unstable medical or neurological illness, including seizures, renal impairment or cerebral vascular accident.
  2. Use of oral contraceptives or other hormonal supplements.
  3. Significant suicidal or homicidal ideation requiring intervention.
  4. Daily use of long or short-acting narcotic medications.
  5. Current Diagnostic and Statistical Manual (DSM-IV) diagnosis of bipolar disorder, schizophrenia, or other psychotic disorder, or cognitive disorder due to a general medical condition (other than if related to mild TBI).
  6. Female patients who are pregnant or breast-feeding.
  7. Known allergy to study medication.
  8. History of moderate or severe TBI (mild TBI is permissible).
  9. DSM-IV criteria met for alcohol and/or other substance abuse or dependence within past three months (excludes caffeine and nicotine).
  10. Have received epidural steroids, facet block, nerve block, or other invasive procedures aimed to reduce low back pain within the past 3 months prior to Visit 1.
  11. Completion of daily diaries for less than 70% of days between Visit 1 and Visit 2 and between Visit 2 and Visit 3.
  12. Have ongoing or anticipated disability compensation or litigation issues, in the best judgment of the investigator.
  13. Have a presence of any factors/conditions, medical or other, that in the judgment of the investigator may interfere with performance of study outcome measures, such as treatment-refractory history.
  14. Have serious or unstable cardiovascular, hepatic, renal, metabolic, respiratory, or hematologic illness, symptomatic peripheral vascular disease, or other medical condition or psychiatric conditions that, in the opinion of investigator and study physician, would compromise participation or be likely to lead to hospitalization during the course of the study.
  15. Are non-ambulatory or require the use of crutches or a walker.
  16. Current suicidal or homicidal ideation necessitating clinical intervention or representing an imminent concern, or history of suicide attempt in the past 3 years.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01898013

Contact: Jennifer C Naylor, PhD 91928600411 ext 3631

United States, North Carolina
Durham VA Medical Center Recruiting
Durham, North Carolina, United States, 27705
Sponsors and Collaborators
Durham VA Medical Center
Principal Investigator: Jennifer C. Naylor, PhD Durham VA Medical Center
Study Director: Christine E Marx, MD Durham VA Medical Center

Responsible Party: Durham VA Medical Center Identifier: NCT01898013     History of Changes
Other Study ID Numbers: 01710
1IK2RX000908-01A1 ( U.S. NIH Grant/Contract )
First Posted: July 12, 2013    Key Record Dates
Last Update Posted: April 21, 2017
Last Verified: April 2017

Keywords provided by Durham VA Medical Center:
clinical trial
low back
placebo controlled

Additional relevant MeSH terms:
Back Pain
Chronic Pain
Low Back Pain
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs