We updated the design of this site on September 25th. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01297335
First Posted: February 16, 2011
Last Update Posted: October 19, 2016
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. Read our disclaimer for details.
Collaborator:
Medtronic
Information provided by (Responsible Party):
The Center for Clinical Research, Winston-Salem, NC
  Purpose
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.

Condition Intervention Phase
Hypertension Drug: clonidine Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Hemodynamic Effect of Intrathecal Clonidine in Hypertensive Subjects: A Pilot Study to Assess Its Effectiveness in Hypertensive Subjects With Poor Blood Pressure Control (Phase II)

Resource links provided by NLM:


Further study details as provided by The Center for Clinical Research, Winston-Salem, NC:

Primary Outcome Measures:
  • Change in Blood Pressure After Intrathecal Injection of Clonidine. [ 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 ]

    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:
  • Likert Scale Pain Rating [ Time Frame: 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 [ Time Frame: 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.


Enrollment: 10
Study Start Date: February 2011
Study Completion Date: July 2012
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Intrathecal 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.
Drug: clonidine
Intrathecal Clonidine
Other Name: catapres

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.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   30 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
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 ClinicalTrials.gov identifier (NCT number): NCT01297335


Sponsors and Collaborators
The Center for Clinical Research, Winston-Salem, NC
Medtronic
Investigators
Principal Investigator: Richard L. Rauck, MD Owner
  More Information

Publications:
Onesti G, Schwartz AB, Kim KE, Swartz C, Brest AN. Pharmacodynamic effects of a new antihypertensive drug, Catapres (ST-155). Circulation. 1969 Feb;39(2):219-28.
Davies DS, Wing AM, Reid JL, Neill DM, Tippett P, Dollery CT. Pharmacokinetics and concentration-effect relationships of intervenous and oral clonidine. Clin Pharmacol Ther. 1977 May;21(5):593-601.
Frisk-Holmberg M, Paalzow L, Wibell L. Relationship between the cardiovascular effects and steady-state kinetics of clonidine in hypertension. Demonstration of a therapeutic window in man. Eur J Clin Pharmacol. 1984;26(3):309-13.
Reid JL, Wing LM, Mathias CJ, Frankel HL, Neill E. The central hypotensive effect of clonidine. Studies in tetraplegic subjects. Clin Pharmacol Ther. 1977 Apr;21(4):375-81.
Brown MJ, Struthers AD, di Silvio L. Peripheral alpha 2 adrenoceptor stimulation contributes to the sympatholytic effect of guanfacine in humans. J Cardiovasc Pharmacol. 1985;7 Suppl 6:S159-61.
Guthrie GP Jr, Kotchen TA. Effects of prazosin and clonidine on sympathetic and baroreflex function in patients with essential hypertension. J Clin Pharmacol. 1983 Aug-Sep;23(8-9):348-54.
Mohanty PK, Sowers JR, McNamara C, Thames MD. Reflex vasoconstrictor responses to cardiopulmonary baroreceptor unloading, head-up tilt, and cold pressor testing in elderly mild-to-moderate hypertensives: effect of clonidine. J Cardiovasc Pharmacol. 1987;10 Suppl 12:S135-7.
Muzi M, Goff DR, Kampine JP, Roerig DL, Ebert TJ. Clonidine reduces sympathetic activity but maintains baroreflex responses in normotensive humans. Anesthesiology. 1992 Nov;77(5):864-71.
Houston MC. Treatment of hypertensive emergencies and urgencies with oral clonidine loading and titration. A review. Arch Intern Med. 1986 Mar;146(3):586-9. Review.
Masotti G, Scarti L, Poggesi L, Bisi G, Gallini C, Neri Serneri GG. Changes in cardiac function after effective treatment of hypertensive emergencies with i.v. clonidine. Eur Heart J. 1984 Dec;5(12):1036-42.
Niarchos AP. Evaluation of intravenous clonidine in hypertensive emergencies. J Clin Pharmacol. 1978 Apr;18(4):220-8.
Magorien RD, Hermiller JB, Unverferth DV, Leier CV. Regional hemodynamic effects of clonidine in congestive heart failure. J Cardiovasc Pharmacol. 1985 Jan-Feb;7(1):91-6.
Zochowski RJ, Lada W. Intravenous clonidine treatment in acute myocardial infarction (with comparison to a nitroglycerin-treated and control group). J Cardiovasc Pharmacol. 1986;8 Suppl 3:S41-5.
Wallace AW, Galindez D, Salahieh A, Layug EL, Lazo EA, Haratonik KA, Boisvert DM, Kardatzke D. Effect of clonidine on cardiovascular morbidity and mortality after noncardiac surgery. Anesthesiology. 2004 Aug;101(2):284-93.
Byrd BF 3rd, Collins HW, Primm RK. Risk factors for severe bradycardia during oral clonidine therapy for hypertension. Arch Intern Med. 1988 Mar;148(3):729-33.
Kibler LE, Gazes PC. Effect of clonidine on atrioventricular conduction. JAMA. 1977 Oct 31;238(18):1930-2.
Toussaint C, Cave D, Saoudi N, Moore N, Letac B. Electrophysiological effects of intravenous clonidine on sinus node function and conduction in man. J Cardiovasc Pharmacol. 1984 Jan-Feb;6(1):56-60.
Clementy J, Castagné D, Wicker P, Dallocchio M, Bricaud H. Study of the electrophysiologic properties of clonidine administered intravenously. J Cardiovasc Pharmacol. 1986;8 Suppl 3:S24-9.
Rupp H, Maisch B, Brilla CG. Drug withdrawal and rebound hypertension: differential action of the central antihypertensive drugs moxonidine and clonidine. Cardiovasc Drugs Ther. 1996 Jun;10 Suppl 1:251-62.
Fuxe K, Tinner B, Bjelke B, Agnati LF, Verhofstad A, Steinbusch HG, Goldstein M, Hersh L, Kalia M. Monoaminergic and Peptidergic Innervation of the Intermedio-Lateral Horn of the Spinal Cord. Eur J Neurosci. 1990;2(5):451-460.
Fuxe K, Tinner B, Bjelke B, Agnati LF, Verhofstad A, Steinbusch HG, Goldstein M, Kalia M. Monoaminergic and Peptidergic Innervation of the Intermedio-Lateral Horn of the Spinal Cord. Eur J Neurosci. 1990;2(5):430-450.
Unnerstall JR, Kopajtic TA, Kuhar MJ. Distribution of alpha 2 agonist binding sites in the rat and human central nervous system: analysis of some functional, anatomic correlates of the pharmacologic effects of clonidine and related adrenergic agents. Brain Res. 1984 Mar;319(1):69-101. Review.
Guyenet PG, Cabot JB. Inhibition of sympathetic preganglionic neurons by catecholamines and clonidine: mediation by an alpha-adrenergic receptor. J Neurosci. 1981 Aug;1(8):908-17.
Stevens CW, Yaksh TL. Time course characteristics of tolerance development to continuously infused antinociceptive agents in rat spinal cord. J Pharmacol Exp Ther. 1989 Oct;251(1):216-23.
Eisenach JC, Tong CY. Site of hemodynamic effects of intrathecal alpha 2-adrenergic agonists. Anesthesiology. 1991 Apr;74(4):766-71.
De Kock M. Site of hemodynamic effects of alpha 2-adrenergic agonists. Anesthesiology. 1991 Oct;75(4):715-6.
Eisenach JC, Hood DD, Curry R. Intrathecal, but not intravenous, clonidine reduces experimental thermal or capsaicin-induced pain and hyperalgesia in normal volunteers. Anesth Analg. 1998 Sep;87(3):591-6.
Kooner JS, Birch R, Frankel HL, Peart WS, Mathias CJ. Hemodynamic and neurohormonal effects of clonidine in patients with preganglionic and postganglionic sympathetic lesions. Evidence for a central sympatholytic action. Circulation. 1991 Jul;84(1):75-83.
Castro MI, Eisenach JC. Pharmacokinetics and dynamics of intravenous, intrathecal, and epidural clonidine in sheep. Anesthesiology. 1989 Sep;71(3):418-25.
Eisenach JC, Lysak SZ, Viscomi CM. Epidural clonidine analgesia following surgery: phase I. Anesthesiology. 1989 Nov;71(5):640-6.
Mendez R, Eisenach JC, Kashtan K. Epidural clonidine analgesia after cesarean section. Anesthesiology. 1990 Nov;73(5):848-52.
Huntoon M, Eisenach JC, Boese P. Epidural clonidine after cesarean section. Appropriate dose and effect of prior local anesthetic. Anesthesiology. 1992 Feb;76(2):187-93.
Eisenach JC, D'Angelo R, Taylor C, Hood DD. An isobolographic study of epidural clonidine and fentanyl after cesarean section. Anesth Analg. 1994 Aug;79(2):285-90.
Chiari A, Lorber C, Eisenach JC, Wildling E, Krenn C, Zavrsky A, Kainz C, Germann P, Klimscha W. Analgesic and hemodynamic effects of intrathecal clonidine as the sole analgesic agent during first stage of labor: a dose-response study. Anesthesiology. 1999 Aug;91(2):388-96.
D'Angelo R, Evans E, Dean LA, Gaver R, Eisenach JC. Spinal clonidine prolongs labor analgesia from spinal sufentanil and bupivacaine. Anesth Analg. 1999 Mar;88(3):573-6.
Rauck RL, Eisenach JC, Jackson K, Young LD, Southern J. Epidural clonidine treatment for refractory reflex sympathetic dystrophy. Anesthesiology. 1993 Dec;79(6):1163-9; discussion 27A.
Eisenach JC, Rauck RL, Buzzanell C, Lysak SZ. Epidural clonidine analgesia for intractable cancer pain: phase I. Anesthesiology. 1989 Nov;71(5):647-52.
Eisenach JC, DuPen S, Dubois M, Miguel R, Allin D. Epidural clonidine analgesia for intractable cancer pain. The Epidural Clonidine Study Group. Pain. 1995 Jun;61(3):391-9.
Eisenach J, Detweiler D, Hood D. Hemodynamic and analgesic actions of epidurally administered clonidine. Anesthesiology. 1993 Feb;78(2):277-87.
Eisenach JC, Hood DD, Tuttle R, Shafer S, Smith T, Tong C. Computer-controlled epidural infusion to targeted cerebrospinal fluid concentrations in humans. Clonidine. Anesthesiology. 1995 Jul;83(1):33-47.
Hood DD, Mallak KA, Eisenach JC, Tong C. Interaction between intrathecal neostigmine and epidural clonidine in human volunteers. Anesthesiology. 1996 Aug;85(2):315-25.
De Kock M, Eisenach J, Tong C, Schmitz AL, Scholtes JL. Analgesic doses of intrathecal but not intravenous clonidine increase acetylcholine in cerebrospinal fluid in humans. Anesth Analg. 1997 Apr;84(4):800-3.
Eisenach JC, Hood DD, Curry R. Relative potency of epidural to intrathecal clonidine differs between acute thermal pain and capsaicin-induced allodynia. Pain. 2000 Jan;84(1):57-64.
Eisenach JC, De Kock M, Klimscha W. alpha(2)-adrenergic agonists for regional anesthesia. A clinical review of clonidine (1984-1995). Anesthesiology. 1996 Sep;85(3):655-74. Review.
Baker A, Klimscha W, Eisenach JC, Li XH, Wildling E, Menth-Chiari WA, Chiari AI. Intrathecal clonidine for postoperative analgesia in elderly patients: the influence of baricity on hemodynamic and analgesic effects. Anesth Analg. 2004 Jul;99(1):128-34.
Nishikawa T, Kimura T, Taguchi N, Dohi S. Oral clonidine preanesthetic medication augments the pressor responses to intravenous ephedrine in awake or anesthetized patients. Anesthesiology. 1991 Apr;74(4):705-10.
Wing LM, Reid JL, Davies DS, Neill EA, Tippett P, Dollery CT. Pharmacokinetic and concentration-effect relationships of clonidine in essential hypertension. Eur J Clin Pharmacol. 1977 Dec 28;12(6):463-9.
Abdelhammed AI, Smith RD, Levy P, Smits GJ, Ferrario CM. Noninvasive hemodynamic profiles in hypertensive subjects. Am J Hypertens. 2005 Feb;18(2 Pt 2):51S-59S.
Ferrario CM. New approaches to hypertension management: always reasonable but now necessary. Am J Hypertens. 2005 Feb;18(2 Pt 2):23S-25S. Review.
Adji A, O'Rourke MF. Determination of central aortic systolic and pulse pressure from the radial artery pressure waveform. Blood Press Monit. 2004 Jun;9(3):115-21.
Lemogoum D, Flores G, Van den Abeele W, Ciarka A, Leeman M, Degaute JP, van de Borne P, Van Bortel L. Validity of pulse pressure and augmentation index as surrogate measures of arterial stiffness during beta-adrenergic stimulation. J Hypertens. 2004 Mar;22(3):511-7.
al'Absi M, Devereux RB, Lewis CE, Kitzman DW, Rao DC, Hopkins P, Markovitz J, Arnett DK. Blood pressure responses to acute stress and left ventricular mass (The Hypertension Genetic Epidemiology Network Study). Am J Cardiol. 2002 Mar 1;89(5):536-40.
Hood DD, Eisenach JC, Tong C, Tommasi E, Yaksh TL. Cardiorespiratory and spinal cord blood flow effects of intrathecal neostigmine methylsulfate, clonidine, and their combination in sheep. Anesthesiology. 1995 Feb;82(2):428-35.
Yaksh TL, Rathbun M, Jage J, Mirzai T, Grafe M, Hiles RA. Pharmacology and toxicology of chronically infused epidural clonidine.HCl in dogs. Fundam Appl Toxicol. 1994 Oct;23(3):319-35.

Responsible Party: The Center for Clinical Research, Winston-Salem, NC
ClinicalTrials.gov Identifier: NCT01297335     History of Changes
Other Study ID Numbers: 1461 Clonidine
1461 ( Other Grant/Funding Number: Medtronic )
First Submitted: February 14, 2011
First Posted: February 16, 2011
Results First Submitted: July 27, 2015
Results First Posted: January 1, 2016
Last Update Posted: October 19, 2016
Last Verified: September 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: no individual's data will be shared with anyone other than the members of the study staff, and the confidentiality will be maintained in accordance with HIPAA rules.

Keywords provided by The Center for Clinical Research, Winston-Salem, NC:
intrathecal
clonidine
poorly
controlled
hypertension

Additional relevant MeSH terms:
Hypertension
Vascular Diseases
Cardiovascular Diseases
Clonidine
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Antihypertensive Agents
Sympatholytics
Autonomic Agents
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action


To Top