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| Name | Class |
|---|---|
| Kettering Health Network | OTHER |
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In this study, subjects with diabetic neuropathic pain (DNP) will be treated for 12 weeks with either placebo, 40 or 80 mg sustained release sodium nitrite (TV1001sr) twice daily. Primary endpoints will be safety and pharmacokinetics. Assessment of the study medications affects on pain following treatment will also be recorded.
This is a dose-ranging study to evaluate the safety, pharmacokinetics, and tolerability of multiple doses of an oral, sustained release formulation of sodium nitrite (TV1001sr) in subjects with DNP. The primary objective is to assess the safety and tolerability of multiple doses of twice daily 40 mg and 80 mg TV1001sr compared with placebo over a 12 week treatment period and the pharmacokinetics of the sustained release formulation of sodium nitrite. Secondary objectives are to evaluate the pharmacokinetics and markers of functional improvement including pain questionnaires, quantitative sensory testing and changes in markers of diabetes.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | One placebo tablet administered twice daily for 12 weeks. |
|
| 40 mg TV1001sr | Active Comparator | One 40 mg enteric coated sustained release, sodium nitrite tablets administered twice daily. |
|
| Placebo (2) | Placebo Comparator | Two placebo tablets administered twice daily for 12 weeks. |
|
| 80 mg TV1001sr | Active Comparator | Two 40 mg enteric coated sustained release, sodium nitrite tablets administered twice daily. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sodium nitrite | Drug | Sustained release formulation of sodium nitrite |
|
| Measure | Description | Time Frame |
|---|---|---|
| Reporting of Adverse Events During 12 Week Study Period | The primary objective of this clinical study is to evaluate the safety and tolerability of multiple doses of twice daily 40mg and 80mg sustained release sodium nitrite compared with placebo over a 12 week treatment period. The following safety parameters will also be assessed: concomitant medication usage, physical examination, vital signs, Comprehensive Metabolic Panel, and complete blood count. Assessment of acute adverse events (i.e., drop in blood pressure, dizziness) after administration of each dose level. Counts are number of subjects reporting at least 1 Adverse Event. The total Adverse Events recorded in each cohort is also reported. | 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetics (Blood Levels of Nitrite) | Blood levels of nitrite will be assessed for 6 hours post-administration on the initial dosing visit. | 1 day |
| The Number of Participants Who Reported Use of Analgesic or Medications for Neuropathic Pain. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Amol Soin, PhD | Ohio Pain Clinic | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Ohio Pain Clinic | Centerville | Ohio | 45458 | United States |
IPD will only be available to the PI of the trial, summary information will be published and shared with other researchers.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | One placebo tablet administered twice daily for 12 weeks. Placebo: Placebo tablets |
| FG001 | 40 mg TV1001sr | One 40 mg enteric coated sustained release, sodium nitrite tablets administered twice daily. Sodium nitrite: Sustained release formulation of sodium nitrite |
| FG002 | Placebo (2) | Two placebo tablets administered twice daily for 12 weeks. Placebo: Placebo tablets |
| FG003 | 80 mg TV1001sr | Two 40 mg enteric coated sustained release, sodium nitrite tablets administered twice daily. Sodium nitrite: Sustained release formulation of sodium nitrite |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | One placebo tablet administered twice daily for 12 weeks. Placebo: Placebo tablets |
| BG001 | 40 mg TV1001sr | One 40 mg enteric coated sustained release, sodium nitrite tablets administered twice daily. Sodium nitrite: Sustained release formulation of sodium nitrite |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| 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 | Reporting of Adverse Events During 12 Week Study Period | The primary objective of this clinical study is to evaluate the safety and tolerability of multiple doses of twice daily 40mg and 80mg sustained release sodium nitrite compared with placebo over a 12 week treatment period. The following safety parameters will also be assessed: concomitant medication usage, physical examination, vital signs, Comprehensive Metabolic Panel, and complete blood count. Assessment of acute adverse events (i.e., drop in blood pressure, dizziness) after administration of each dose level. Counts are number of subjects reporting at least 1 Adverse Event. The total Adverse Events recorded in each cohort is also reported. | Randomized population including dropouts. | Posted | Number | Adverse Events | 12 weeks |
|
9 months
Asked subjects at each phone call and visit to report any adverse event.
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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 | Combined Placebo | A combination of the once/day and twice/day placebo groups. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hyponatremia | Blood and lymphatic system disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headaches | Nervous system disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Tony Giordano | TheraVasc Inc. | 3183493851 | tgiordano@theravasc.com |
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| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| ID | Term |
|---|---|
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
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| ID | Term |
|---|---|
| D012977 | Sodium Nitrite |
| ID | Term |
|---|---|
| D009573 | Nitrites |
| D009608 | Nitrous Acid |
| D017672 | Nitrogen Compounds |
| D007287 | Inorganic Chemicals |
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| Placebo | Drug | Placebo tablets containing same excipients and coatings used in the active tablets, without sodium nitrite being added. |
|
Daily patient reported use of analgesic or medications for neuropathic pain. The use of medications were recorded at the baseline visit and during both the intermediate and final visit for each subject. All subjects used at least one prescription pain medication, other than one subject in the 80-mg dose cohort who used only ibuprofen to control pain. Most subjects used more than one prescription pain medication. There was no change in use of pain medications during the trial period.
| 12 weeks |
| Assessment of Patients Reported Pain Through Composite Analysis of Pain Questionaires. | Subjects completed the Brief pain inventory (BPI), RAND 36 questionnaire, neuropathic pain symptom inventory (NPSI) and Short Form McGill Pain Questionnaire at each visit for these self-reported questionnaires. The BPI is a questionnaire that measures the patient's subjective perception of pain, its exacerbating and alleviating factors, and perceived effect on functional status; the NPSI is a questionnaire that measures the symptoms associated with neuropathic pain; the Short Form McGill Questionnaire subjectively assesses the patients perception of pain described by commonly used adjectives associated with pain. NPSI is average of 12 questions, range from 0 (no pain) to 120 (maximal pain); For BPI severity and interference, questions are scored from 0-10, then there average score for each subsection is calculated (the higher the score, the worse the response); Scores on McGill range from 0-10, lower associated for less pain, then averaged for each sub score and total score. | Baseline (visit 1) and 12 weeks (visit 3) |
| Clinical Assessment of Pain. (Quantitative Sensory Testing) | Quantitative sensory testing (QST) was conducted at each visit to determine patients sensitivity to pain. QST was assessed using a quantitative nerve conductance machine where nerves in the distal extremity are subjected to electrical stimulation to determine the sensory threshold of the skin. Nerve conductance measures how fast an electrical impulse moves through the nerve, and nerve velocity measures the speed at which an electrical impulse moves down a neuronal pathway. | 12 weeks |
| Assessment of Diabetes. (HbA1C Levels) | HbA1C levels will be monitored at each visit to determine whether treatment reduces circulating glucose levels. | 12 weeks |
| Assessment of Blood Oxygenation. (Pulse Oximetry) | Pulse oximetry will be used at each visit to determine whether treatment improves oxygen levels in the blood. | 12 weeks |
| Physician Decision |
|
| BG002 | Placebo (2) | Two placebo tablets administered twice daily for 12 weeks. Placebo: Placebo tablets |
| BG003 | 80 mg TV1001sr | Two 40 mg enteric coated sustained release, sodium nitrite tablets administered twice daily. Sodium nitrite: Sustained release formulation of sodium nitrite |
| BG004 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | 40 mg TV1001sr | Treatment twice daily with 40 mg sustained release sodium nitrite |
| OG002 | 80 mg TV1001sr | Treatment with 80 mg (2 x 40 mg tablets) twice daily with sustained release sodium nitrite |
|
|
| Secondary | Pharmacokinetics (Blood Levels of Nitrite) | Blood levels of nitrite will be assessed for 6 hours post-administration on the initial dosing visit. | All subjects who were randomized. | Posted | Mean | Standard Deviation | ng/ml | 1 day |
|
|
|
|
| Secondary | The Number of Participants Who Reported Use of Analgesic or Medications for Neuropathic Pain. | Daily patient reported use of analgesic or medications for neuropathic pain. The use of medications were recorded at the baseline visit and during both the intermediate and final visit for each subject. All subjects used at least one prescription pain medication, other than one subject in the 80-mg dose cohort who used only ibuprofen to control pain. Most subjects used more than one prescription pain medication. There was no change in use of pain medications during the trial period. | Analyzed only those subjects who completed 12 weeks of testing. | Posted | Count of Participants | Participants | 12 weeks |
|
|
|
| Secondary | Assessment of Patients Reported Pain Through Composite Analysis of Pain Questionaires. | Subjects completed the Brief pain inventory (BPI), RAND 36 questionnaire, neuropathic pain symptom inventory (NPSI) and Short Form McGill Pain Questionnaire at each visit for these self-reported questionnaires. The BPI is a questionnaire that measures the patient's subjective perception of pain, its exacerbating and alleviating factors, and perceived effect on functional status; the NPSI is a questionnaire that measures the symptoms associated with neuropathic pain; the Short Form McGill Questionnaire subjectively assesses the patients perception of pain described by commonly used adjectives associated with pain. NPSI is average of 12 questions, range from 0 (no pain) to 120 (maximal pain); For BPI severity and interference, questions are scored from 0-10, then there average score for each subsection is calculated (the higher the score, the worse the response); Scores on McGill range from 0-10, lower associated for less pain, then averaged for each sub score and total score. | NPS is a sum of total scores, McGill and BPI an average of the scores for each question. | Posted | Mean | Full Range | units on a scale | Baseline (visit 1) and 12 weeks (visit 3) |
|
|
|
|
| Secondary | Clinical Assessment of Pain. (Quantitative Sensory Testing) | Quantitative sensory testing (QST) was conducted at each visit to determine patients sensitivity to pain. QST was assessed using a quantitative nerve conductance machine where nerves in the distal extremity are subjected to electrical stimulation to determine the sensory threshold of the skin. Nerve conductance measures how fast an electrical impulse moves through the nerve, and nerve velocity measures the speed at which an electrical impulse moves down a neuronal pathway. | Analyzed only the subjects that completed testing. | Posted | Mean | Standard Deviation | meters per second | 12 weeks |
|
|
|
|
| Secondary | Assessment of Diabetes. (HbA1C Levels) | HbA1C levels will be monitored at each visit to determine whether treatment reduces circulating glucose levels. | HbA1c blood levels were analyzed at baseline, V2 and V3 | Posted | Mean | Standard Deviation | percentage of glycosylated hemoglobin | 12 weeks |
|
|
|
|
| Secondary | Assessment of Blood Oxygenation. (Pulse Oximetry) | Pulse oximetry will be used at each visit to determine whether treatment improves oxygen levels in the blood. | Oxygen saturation was measured at baseline, V2 and V3. | Posted | Mean | Standard Deviation | % Oxygenation | 12 weeks |
|
|
|
|
| 0 |
| 9 |
| 2 |
| 9 |
| 9 |
| 9 |
| EG001 | 40 mg TV1001sr | Treatment twice daily with 40 mg sustained release sodium nitrite | 0 | 8 | 2 | 8 | 8 | 8 |
| EG002 | 80 mg TV1001sr | Treatment with 80 mg (2 x 40 mg tablets) twice daily with sustained release sodium nitrite | 0 | 9 | 2 | 8 | 7 | 9 |
| Hyperglycemia | Blood and lymphatic system disorders | Systematic Assessment |
|
| Chest pains | Cardiac disorders | Systematic Assessment |
|
| Febrile illness | Infections and infestations | Systematic Assessment |
|
| Dizziness | Nervous system disorders | Systematic Assessment |
|
| Urinary Disorders | Renal and urinary disorders | Systematic Assessment |
|
| Ulcers | Gastrointestinal disorders | Systematic Assessment |
|
| Swelling | General disorders | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | Systematic Assessment |
|
| Fatigue | Nervous system disorders | Systematic Assessment |
|
| Dry Mouth | General disorders | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Systematic Assessment |
|
| Numbness | Nervous system disorders | Systematic Assessment |
|
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| D017670 |
| Sodium Compounds |
|
| Subjects using Lyrica |
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| Subjects using Morphine |
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| Subjects using Tramadol |
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| Subjects using Cymbalta |
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| Subjects using Flexeril |
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| Subjects using Naproxen |
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| Subjects using Percocet |
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| Subjects using Vicodin |
|
|
| BPI: Severity Score-V1 |
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| BPI: Severity Score-V3 |
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| BPI: Interferrence-V1 |
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| BPI: Interferrence-V3 |
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| McGill: Total-V1 |
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| McGill: Total-V3 |
|
| McGill: Continuous-V1 |
|
| McGill: Continuous-V3 |
|
| McGill: Intermittent-V1 |
|
| McGill: Intermittent-V3 |
|
|
| Nerve Conductance: V3 |
|
| Nerve Velocity: Baseline |
|
| Nerve Velocity: V2 |
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| Nerve Velocity: V3 |
|
|
| V3 |
|
|
| V3 |
|