Lower Back PainPhase 2NCT01898013
Neurosteroids as Novel Therapeutic Agents for Chronic Pain in OEF/OIF Veterans
A Phase 2 study testing Pregnenolone in people with Lower Back Pain, run by Durham VA Medical Center at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Lower Back Pain
- What is being tested?
- Pregnenolone
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 94 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Sep 2013to 3 Apr 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- OEF/OIF Veterans, 18-65 years of age, with chronic low back pain.
- 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).
- Have a weekly mean of 24-hour average pain score ≥ 4 at baseline.
- 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.
- No change in medications less than 4 weeks before baseline.
- 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).
- Ability to fully participate in the informed consent process.
Who cannot join
- Unstable medical or neurological illness, including seizures, renal impairment or cerebral vascular accident.
- Use of oral contraceptives or other hormonal supplements.
- Significant suicidal or homicidal ideation requiring intervention.
- Daily use of long or short-acting narcotic medications.
- 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).
- Female patients who are pregnant or breast-feeding.
Show all 16Show fewer
- Known allergy to study medication.
- History of moderate or severe TBI (mild TBI is permissible).
- DSM-IV criteria met for alcohol and/or other substance abuse or dependence within past three months (excludes caffeine and nicotine).
- 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.
- Completion of daily diaries for less than 70% of days between Visit 1 and Visit 2 and between Visit 2 and Visit 3.
- Have ongoing or anticipated disability compensation or litigation issues, in the best judgment of the investigator.
- 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.
- 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.
- Are non-ambulatory or require the use of crutches or a walker.
- Current suicidal or homicidal ideation necessitating clinical intervention or representing an imminent concern, or history of suicide attempt in the past 3 years.
Trial locations and contacts
1 site in 1 country.
United States1 site
Durham VA Medical Center
Durham, North Carolina, 27705
About this study
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).
- Conditions
- Lower Back Pain
- Being tested
- Pregnenolone, Placebo
- Keywords
- pain, pregnenolone, Veterans, clinical trial, neurosteroid, allopregnanolone, low back, placebo controlled, randomized, musculoskeletal
- Medical subject headings
- Low Back Pain, Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PregnenoloneDrug
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Pregnenolone | Active comparator | 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. Receives: Drug: Pregnenolone |
| Placebo | Placebo comparator | 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Pain Intensity Rating (Visit 6-Baseline)
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). The outcome measure is the change in scores before and after treatment. That is, the baseline and Visit 6 difference scores.
Measured: Difference Scores (Visit 6-Baseline)
Secondary outcomes (5)
Change in Pain Interference Scores (Visit 6-Baseline)
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. The outcome measure is the change in scores before and after treatment. That is, the baseline and Visit 6 difference scores.
Measured: Difference Scores of Averaged Pain Interference Domains (Visit 6-Baseline)
Change in Beck Depression Inventory (Visit 6-Baseline)
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). The outcome measure is the change in scores before and after treatment. That is, the baseline and Visit 6 difference scores.
Measured: Difference Scores of BDI (Visit 6-Baseline)
Change in Davidson Trauma Scale (Visit 6-Baseline)
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). The outcome measure is the change in scores before and after treatment. That is, the baseline and Visit 6 difference scores.
Measured: Difference Scores of Total DTS Scores (Visit 6-Baseline)
Change in Tower of London (Visit 6-Baseline)
The Tower of London is a clinician administered subtest from the Brief Assessment of Cognition-Affect (BAC-A) which measures executive functioning. Participants were shown two pictures simultaneously. Each picture showed three balls of different colors arranged on three pegs, with the balls in a unique arrangement in each picture. Participants were asked to give the total number of times the balls in one picture need to be moved in order to make the arrangement of balls identical to that of the other, opposing picture. There were 20 trials, 2 more were added if all 10 prior trials were correct. Range of scores was 0-22, higher scores are better. Z scores calculated and reported. The outcome measure is the change in Z scores before and after treatment. That is, the baseline and Visit 6 difference scores.
Measured: Difference Z-Score (Visit 6-Baseline)
Change in Digit Sequence (Visit 6-Baseline)
Digit Sequencing Task is a clinician administered subtest from the Brief Assessment of Cognition-Affect (BAC-A) which measures working memory and attention. Participants were presented with clusters of numbers of increasing length.They were asked to tell the experimenter the numbers in order, from lowest to highest. Measures: number of correct responses (range: 0-28, higher is better). Scores converted to Z-scores. The outcome measure is the change in Z scores before and after treatment. That is, the baseline and Visit 6 difference scores.
Measured: Difference Z-Scores (Visit 6-Baseline)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2013 (estimated)
- Study start13 Sep 2013
- Primary completion3 Apr 2017
- Study completion3 Apr 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Lower Back PainStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 94 participants (actual)
Sponsor and investigators
- Lead sponsor
- Durham VA Medical Center
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Jennifer C. Naylor, PhD, Principal investigator, Durham VA Medical CenterChristine E Marx, MD, Study director, Durham VA Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01898013
- Sponsor's protocol ID
- 01710
- Other IDs
- 1IK2RX000908-01A1
- Status last verified
- Sep 2018
- First submitted
- 8 Jul 2013
- Last updated
- 3 Oct 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Naylor JC, Kilts JD, Shampine LJ, Parke GJ, Wagner HR, Szabo ST, Smith KD, Allen TB, Telford-Marx EG, Dunn CE, Cuffe BT, O'Loughlin SH, Marx CE. Effect of Pregnenolone vs Placebo on Self-reported Chronic Low Back Pain Among US Military Veterans: A Randomized Clinical Trial. JAMA Netw Open. 2020 Mar 2;3(3):e200287. doi: 10.1001/jamanetworkopen.2020.0287.
PubMed 32119096
Study at a glance
From the registry record, last updated by the sponsor on 3 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neurosteroids as Novel Therapeutic Agents for Chronic Pain in OEF/OIF Veterans
- ClinicalTrials.gov ID
- NCT01898013
- Acronym / sponsor ID
- 01710
- Conditions
- Lower Back Pain
- Keywords
- pain, pregnenolone, Veterans, clinical trial, neurosteroid, allopregnanolone, low back, placebo controlled
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 94 participants (actual)
- Lead sponsor
- Durham VA Medical CenterUS federal agency
- Study start
- 13 Sep 2013 (actual)
- Primary completion
- 3 Apr 2017 (actual)
- Study completion
- 3 Apr 2017 (actual)
- First posted
- 12 Jul 2013 (estimated)
- Results
- Posted 3 Oct 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pregnenolone | Active comparator | Drug: PregnenolonePregnenolone 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. |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- OEF/OIF Veterans, 18-65 years of age, with chronic low back pain.
- 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).
- Have a weekly mean of 24-hour average pain score ≥ 4 at baseline.
- 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.
- No change in medications less than 4 weeks before baseline.
Key exclusion criteria (16 listed)
- Unstable medical or neurological illness, including seizures, renal impairment or cerebral vascular accident.
- Use of oral contraceptives or other hormonal supplements.
- Significant suicidal or homicidal ideation requiring intervention.
- Daily use of long or short-acting narcotic medications.
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pregnenolone | Drug | Pregnenolone |
| Placebo | Drug | Placebo |
Primary outcome
Change in Pain Intensity Rating (Visit 6-Baseline)
Time frame: Difference Scores (Visit 6-Baseline)
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). The outcome measure is the change in scores before and after treatment. That is, the baseline and Visit 6 difference scores.
5 secondary outcomes
Change in Pain Interference Scores (Visit 6-Baseline)
Time frame: Difference Scores of Averaged Pain Interference Domains (Visit 6-Baseline)
Change in Beck Depression Inventory (Visit 6-Baseline)
Time frame: Difference Scores of BDI (Visit 6-Baseline)
Change in Davidson Trauma Scale (Visit 6-Baseline)
Time frame: Difference Scores of Total DTS Scores (Visit 6-Baseline)
Change in Tower of London (Visit 6-Baseline)
Time frame: Difference Z-Score (Visit 6-Baseline)
Change in Digit Sequence (Visit 6-Baseline)
Time frame: Difference Z-Scores (Visit 6-Baseline)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Oct 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32119096Naylor JC, Kilts JD, Shampine LJ, Parke GJ, Wagner HR, Szabo ST, Smith KD, Allen TB, Telford-Marx EG, Dunn CE, Cuffe BT, O'Loughlin SH, Marx CE. Effect of Pregnenolone vs Placebo on Self-reported Chronic Low Back Pain Among US Military Veterans: A Randomized Clinical Trial. JAMA Netw Open. 2020 Mar 2;3(3):e200287. doi: 10.1001/jamanetworkopen.2020.0287.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jennifer C. Naylor, PhD principal investigator
Durham VA Medical Center
Christine E Marx, MD study director
Durham VA Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pregnenolone in people with Lower Back Pain, run by Durham VA Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Oct 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Pain Intensity Rating (Visit 6-Baseline) (time frame: Difference Scores (Visit 6-Baseline)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01898013, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Oct 2018.