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

NCT01297335 | Completed Phase 2 Results DMC

• 2 other identifiers: 1461 Clonidine1461
• Study Type: interventional
• Target: 10
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Hypertension

Keywords

intrathecal; clonidine; poorly; controlled; hypertension

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline, Every 10 Minutes for first hour after clonidine injection, and every 15 minutes after first hour, until 4 hours after clonidine injection

Secondary Outcomes (2)

• Likert Scale Pain Rating

  Pre-dose and 1 hour post injection.

• 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.

Study Arms (1)

Intrathecal Clonidine

EXPERIMENTAL

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

Interventions

clonidine DRUG

Intrathecal Clonidine

Also known as: catapres

Intrathecal Clonidine

Eligibility Criteria

• Age: 30 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• The Center for Clinical Research, Winston-Salem, NC: lead
• Medtronic: collaborator

Related Publications (54)

• 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. doi: 10.1161/01.cir.39.2.219. No abstract available.

  PMID: 4884576 BACKGROUND

• 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. doi: 10.1002/cpt1977215593.

  PMID: 870272 BACKGROUND

• 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. doi: 10.1007/BF00548760.

  PMID: 6734692 BACKGROUND

• 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. doi: 10.1002/cpt1977214375.

  PMID: 321174 BACKGROUND

• 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. doi: 10.1097/00005344-198500076-00027.

  PMID: 2414580 BACKGROUND

• 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. doi: 10.1002/j.1552-4604.1983.tb02747.x.

  PMID: 6630584 BACKGROUND

• 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.

  PMID: 2455165 BACKGROUND

• 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. doi: 10.1097/00000542-199211000-00005.

  PMID: 1443738 BACKGROUND

• 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.

  PMID: 3513726 BACKGROUND

• 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. doi: 10.1093/oxfordjournals.eurheartj.a061605.

  PMID: 6534750 BACKGROUND

• Niarchos AP. Evaluation of intravenous clonidine in hypertensive emergencies. J Clin Pharmacol. 1978 Apr;18(4):220-8. doi: 10.1002/j.1552-4604.1978.tb01596.x.

  PMID: 632367 BACKGROUND

• 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. doi: 10.1097/00005344-198501000-00015.

  PMID: 2580157 BACKGROUND

• 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.

  PMID: 2429112 BACKGROUND

• 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. doi: 10.1097/00000542-200408000-00007.

  PMID: 15277909 BACKGROUND

• 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.

  PMID: 3341873 BACKGROUND

• Kibler LE, Gazes PC. Effect of clonidine on atrioventricular conduction. JAMA. 1977 Oct 31;238(18):1930-2.

  PMID: 578552 BACKGROUND

• 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.

  PMID: 6199612 BACKGROUND

• Clementy J, Castagne 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. doi: 10.1097/00005344-198608003-00007.

  PMID: 2429109 BACKGROUND

• 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. doi: 10.1007/BF00120495.

  PMID: 8827948 BACKGROUND

• 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. doi: 10.1111/j.1460-9568.1990.tb00436.x.

  PMID: 12106031 BACKGROUND

• 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. doi: 10.1111/j.1460-9568.1990.tb00435.x.

  PMID: 12106030 BACKGROUND

• 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. doi: 10.1016/0165-0173(84)90030-4.

  PMID: 6324960 BACKGROUND

• 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. doi: 10.1523/JNEUROSCI.01-08-00908.1981.

  PMID: 6286903 BACKGROUND

• 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.

  PMID: 2795458 BACKGROUND

• Eisenach JC, Tong CY. Site of hemodynamic effects of intrathecal alpha 2-adrenergic agonists. Anesthesiology. 1991 Apr;74(4):766-71. doi: 10.1097/00000542-199104000-00021.

  PMID: 1672580 BACKGROUND

• De Kock M. Site of hemodynamic effects of alpha 2-adrenergic agonists. Anesthesiology. 1991 Oct;75(4):715-6. doi: 10.1097/00000542-199110000-00046. No abstract available.

  PMID: 1928792 BACKGROUND

• 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. doi: 10.1097/00000539-199809000-00018.

  PMID: 9728835 BACKGROUND

• 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. doi: 10.1161/01.cir.84.1.75.

  PMID: 2060125 BACKGROUND

• Castro MI, Eisenach JC. Pharmacokinetics and dynamics of intravenous, intrathecal, and epidural clonidine in sheep. Anesthesiology. 1989 Sep;71(3):418-25. doi: 10.1097/00000542-198909000-00018.

  PMID: 2774269 BACKGROUND

• Eisenach JC, Lysak SZ, Viscomi CM. Epidural clonidine analgesia following surgery: phase I. Anesthesiology. 1989 Nov;71(5):640-6. doi: 10.1097/00000542-198911000-00003.

  PMID: 2817456 BACKGROUND

• Mendez R, Eisenach JC, Kashtan K. Epidural clonidine analgesia after cesarean section. Anesthesiology. 1990 Nov;73(5):848-52. doi: 10.1097/00000542-199011000-00009.

  PMID: 2240674 BACKGROUND

• 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. doi: 10.1097/00000542-199202000-00005.

  PMID: 1736694 BACKGROUND

• 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. doi: 10.1213/00000539-199408000-00014.

  PMID: 7639365 BACKGROUND

• 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. doi: 10.1097/00000542-199908000-00012.

  PMID: 10443601 BACKGROUND

• 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. doi: 10.1097/00000539-199903000-00020.

  PMID: 10072008 BACKGROUND

• 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.

  PMID: 8267190 BACKGROUND

• Eisenach JC, Rauck RL, Buzzanell C, Lysak SZ. Epidural clonidine analgesia for intractable cancer pain: phase I. Anesthesiology. 1989 Nov;71(5):647-52. doi: 10.1097/00000542-198911000-00004.

  PMID: 2817457 BACKGROUND

• Eisenach JC, DuPen S, Dubois M, Miguel R, Allin D; Epidural Clonidine Study Group. Epidural clonidine analgesia for intractable cancer pain. The Epidural Clonidine Study Group. Pain. 1995 Jun;61(3):391-399. doi: 10.1016/0304-3959(94)00209-W.

  PMID: 7478682 BACKGROUND

• Eisenach J, Detweiler D, Hood D. Hemodynamic and analgesic actions of epidurally administered clonidine. Anesthesiology. 1993 Feb;78(2):277-87. doi: 10.1097/00000542-199302000-00011.

  PMID: 8439023 BACKGROUND

• 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. doi: 10.1097/00000542-199507000-00005.

  PMID: 7605017 BACKGROUND

• 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. doi: 10.1097/00000542-199608000-00013.

  PMID: 8712447 BACKGROUND

• 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. doi: 10.1097/00000539-199704000-00019.

  PMID: 9085961 BACKGROUND

• 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. doi: 10.1016/S0304-3959(99)00181-5.

  PMID: 10601673 BACKGROUND

• 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. doi: 10.1097/00000542-199609000-00026. No abstract available.

  PMID: 8853097 BACKGROUND

• 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):128-134. doi: 10.1213/01.ANE.0000114549.17864.36.

  PMID: 15281518 BACKGROUND

• 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. doi: 10.1097/00000542-199104000-00014.

  PMID: 2008952 BACKGROUND

• 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. doi: 10.1007/BF00561067.

  PMID: 598422 BACKGROUND

• 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. doi: 10.1016/j.amjhyper.2004.11.043.

  PMID: 15752933 BACKGROUND

• Ferrario CM. New approaches to hypertension management: always reasonable but now necessary. Am J Hypertens. 2005 Feb;18(2 Pt 2):23S-25S. doi: 10.1016/j.amjhyper.2004.11.042. No abstract available.

  PMID: 15752930 BACKGROUND

• 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. doi: 10.1097/01.mbp.0000132426.32886.e0.

  PMID: 15199304 BACKGROUND

• 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. doi: 10.1097/00004872-200403000-00013.

  PMID: 15076156 BACKGROUND

• 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. doi: 10.1016/s0002-9149(01)02305-0.

  PMID: 11867037 BACKGROUND

• 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. doi: 10.1097/00000542-199502000-00013.

  PMID: 7856901 BACKGROUND

• 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. doi: 10.1006/faat.1994.1112.

  PMID: 7835532 BACKGROUND

MeSH Terms

Conditions

Hypertension

Interventions

Clonidine

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Imidazolines; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

This study was limited by small sample size, and lack of control group.

Results Point of Contact

• Title: Medical Director
• Organization: The Center for Clinical Research

rrauck@ccrpain.com

3367656181

Study Officials

• Richard L. Rauck, MD

  Owner

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2011
• First Posted: February 16, 2011
• Study Start: February 1, 2011
• Primary Completion: July 1, 2012
• Study Completion: July 1, 2012
• Last Updated: October 19, 2016
• Results First Posted: January 1, 2016

Record last verified: 2016-09

Data Sharing

• IPD Sharing: Will not share