Hypertension
Conditions
Keywords
intrathecal, clonidine, poorly, controlled, hypertension
Brief summary
The purpose of this study is to determine the acute efficacy of intrathecal clonidine to reduce blood pressure in hypertensive subjects with poor blood pressure control and describe its effects on cardiovascular function.
Detailed description
Hypertension occurs commonly, is associated with major morbidity and mortality, and responds poorly to current therapies in a small minority of compliant patients. The goal of this investigator-initiated study is to determine whether intrathecal administration of clonidine reduces blood pressure in hypertensive patients, focusing on a group who often achieve inadequate blood pressure control with multiple drug therapy. After consent, pts will be screened and if qualified brought into center and intrathecal injection of clonidine given. Patients will be closely monitored for 4 hours, while data is collected.
Interventions
DRUGclonidine
Intrathecal Clonidine
Sponsors
Medtronic
The Center for Clinical Research, Winston-Salem, NC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
30 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* Diagnosis of Hypertension * Stable systolic blood pressure \>140 mmHg and \< 190 mmHg * On 3 or more antihypertensive medications * On a diuretic * Patients must be able to understand the risks
Exclusion criteria
* Allergy to clonidine * Presently on clonidine orally or transdermally * Known or suspected correctable causes of secondary hypertension * Breast Feeding or Pregnant women * Unstable Ischemic Heart Disease * Unstable Angina * Intracoronary Stent Placement * Coronary bypass within last 6 months * Myocardial Infarction within last 6 months * Congestive Failure * Cardiac Arrhythmias * Known Cerebral Vascular Disease * Renal Disease * Evidence of Injection Site Infection * Known Bleeding Disorders * Hepatic Insufficiency * Renal Insufficiency * Participation in an investigational drug study within 30 day of enrollment * Prohibited Medications: * Clonidine * Yohimbine * Tricyclic Antidepressants * Mirtazapine * Digitalis * Reserpine * Guanethidine * Non-Steroidal Anti-inflammatory Medication * Alcohol or Barbiturates within 48 hours of study procedure
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Blood Pressure After Intrathecal Injection of Clonidine. | Baseline, Every 10 Minutes for first hour after clonidine injection, and every 15 minutes after first hour, until 4 hours after clonidine injection | Subjects baseline blood pressure (systolic blood pressure (SBP), and diastolic blood pressure (DBP)), and blood pressures after clonidine injection was compared against baseline to assess efficacy of clonidine in refractory hypertensive subjects. Subject's blood pressure was monitored continuously after intrathecal injection of clonidine until subjects blood pressure nadir and return to pre clonidine injection level. The mean value reported below are the average changes in blood pressure from baseline (pre clonidine injection) in both SBP and DBP during post clonidine injection blood pressure monitoring for 4 hours. Blood pressure measurements were collected every 10 minutes for first hour after injection, and every 15 minutes after the first hour, up to 4 hours were averaged to report the change from baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Likert Scale Pain Rating | Pre-dose and 1 hour post injection. | Likert scale is 11 point digital pain rating system that asks subjects to rate their pain from 0 to 10. Rating of 0 means no pain at all, and in increasing order, 10 would mean worst pain imaginable/ unbearable pain. |
| Changes in Visual Analogue Scale (VAS) Ratings of Sedation and Sensation of Dry Mouth Reported by the Subjects, Pre and 1 Hour Post Injection | Before clonidine injection (Baseline), and at 1 hour after clonidine injection. | Subjects were asked to rate severity of two of the most common side effects of clonidine, sedation and sensation of dry mouth, at pre and post (1 hour after) intrathecal administration of clonidine. The mean changes between pre and post injection VAS ratings of sedation and sensation of dry mouth are reported below. The VAS scale ranges from 1 to 10 cm, with higher values indicating higher level of sedation and higher level of dry mouth. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Intrathecal Clonidine All subjects met all inclusion and exclusionary criteria, and we report study subjects' demographic information in following sections. | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | Intrathecal Clonidine |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants |
| Age, Continuous | 57 years STANDARD_DEVIATION 5 |
| Duration of Hypertension Diagnosis | 17 years |
| Number of active antihypertensive medications 3 active antihypertensive medications | 2 participants |
| Number of active antihypertensive medications 4 active antihypertensive medications | 8 participants |
| Race/Ethnicity, Customized African American, Non-hispanic | 7 participants |
| Race/Ethnicity, Customized White, Non-hispanic | 3 participants |
| Region of Enrollment United States | 10 participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 10 |
| serious Total, serious adverse events | 0 / 10 |
Outcome results
Primary
Change in Blood Pressure After Intrathecal Injection of Clonidine.
Subjects baseline blood pressure (systolic blood pressure (SBP), and diastolic blood pressure (DBP)), and blood pressures after clonidine injection was compared against baseline to assess efficacy of clonidine in refractory hypertensive subjects. Subject's blood pressure was monitored continuously after intrathecal injection of clonidine until subjects blood pressure nadir and return to pre clonidine injection level. The mean value reported below are the average changes in blood pressure from baseline (pre clonidine injection) in both SBP and DBP during post clonidine injection blood pressure monitoring for 4 hours. Blood pressure measurements were collected every 10 minutes for first hour after injection, and every 15 minutes after the first hour, up to 4 hours were averaged to report the change from baseline.
Time frame: Baseline, Every 10 Minutes for first hour after clonidine injection, and every 15 minutes after first hour, until 4 hours after clonidine injection
Population: All subjects met inclusion and exclusionary criteria, and was given an intrathecal injection of clonidine. They were followed for changes in blood pressure for 4 hours.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Intrathecal Clonidine | Change in Blood Pressure After Intrathecal Injection of Clonidine. | Change in mean SBP after clonidine injection | 79 mm Hg | Standard Deviation 28 |
| Intrathecal Clonidine | Change in Blood Pressure After Intrathecal Injection of Clonidine. | Change in DBP after clonidine injection | 37 mm Hg | Standard Deviation 17 |
Secondary
Changes in Visual Analogue Scale (VAS) Ratings of Sedation and Sensation of Dry Mouth Reported by the Subjects, Pre and 1 Hour Post Injection
Subjects were asked to rate severity of two of the most common side effects of clonidine, sedation and sensation of dry mouth, at pre and post (1 hour after) intrathecal administration of clonidine. The mean changes between pre and post injection VAS ratings of sedation and sensation of dry mouth are reported below. The VAS scale ranges from 1 to 10 cm, with higher values indicating higher level of sedation and higher level of dry mouth.
Time frame: Before clonidine injection (Baseline), and at 1 hour after clonidine injection.
Population: All qualified subjects were given intrathecal clonidine and were asked to rate level of sedation and sensation of dry mouth before clonidine injection (baseline) and 1 hour post injection on VAS scale.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Intrathecal Clonidine | Changes in Visual Analogue Scale (VAS) Ratings of Sedation and Sensation of Dry Mouth Reported by the Subjects, Pre and 1 Hour Post Injection | Change in level of sedation | 3.36 cm | Standard Deviation 3.66 |
| Intrathecal Clonidine | Changes in Visual Analogue Scale (VAS) Ratings of Sedation and Sensation of Dry Mouth Reported by the Subjects, Pre and 1 Hour Post Injection | Change in sensation of dry mouth | 3.47 cm | Standard Deviation 3.93 |
Secondary
Likert Scale Pain Rating
Likert scale is 11 point digital pain rating system that asks subjects to rate their pain from 0 to 10. Rating of 0 means no pain at all, and in increasing order, 10 would mean worst pain imaginable/ unbearable pain.
Time frame: Pre-dose and 1 hour post injection.
Population: All subjects met inclusion and exclusionary criteria, and received intrathecal injection of clonidine. Subjects were asked to rate their baseline pain on Likert scale prior to receiving intrathecal clonidine injection, and 1 hour post intrathecal clonidine injection.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Intrathecal Clonidine | Likert Scale Pain Rating | Pre-injection average Likert score | 6.5 units on a scale | Standard Deviation 1.9 |
| Intrathecal Clonidine | Likert Scale Pain Rating | Post-injection average Likert score | 3.6 units on a scale | Standard Deviation 2.6 |