Effect of Intrathecal Clonidine in Hypertensive Subjects With Poorly Controlled Blood Pressure

Phase 2

Completed

• Conditions: Hypertension
• Interventions: Drug: clonidine

• Registration Number: NCT01297335
• Lead Sponsor: The Center for Clinical Research, Winston-Salem, NC

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.

Study Timeline

• Study Start: 2011-02
• Study First Submitted: 2011-02-14
• Study First Submitted QC: 2011-02-15
• Study First Posted: 2011-02-16
• Primary Completion: 2012-07
• Study Completion: 2012-07
• Results First Submitted: 2015-07-27
• Results First Submitted QC: 2015-11-30
• Results First Posted: 2016-01-01
• Status Verified: 2016-09
• Last Update Submitted: 2016-09-01
• Last Update Posted: 2016-10-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 10

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Intrathecal Clonidine	clonidine	Subject will receive one time Clonidine injection via lower lumber interspace. Clonidine (Duraclon), 100 μg/ml, 1.5 ml will be diluted to 2 ml with preservative free saline, and total of 150 μg will be delivered. Supine and sitting blood pressures and heart rate will be measured at 10 minute intervals until 60 minutes after clonidine administration, then at 15 minutes for next 3 hours.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.