Comparison of Tandospirone, Amlodipine and Their Combination in Adults With Hypertension and Anxiety

Comparison of Tandospirone, Amlodipine and Their Combination in Adults With Hypertension and Anxiety: a Multicentre, Randomized, Double-blind, Double-dummy, Placebo-controlled Trial

This study compares the antihypertensive effects between different treatment groups including antihypertensive drug, anxiolytic, and both, which provide a new clinical evidence for controlling blood pressure in patients with hypertension and anxiety.

Study Overview

• Status: Unknown
• Conditions: Hypertension; Anxiety
• Intervention / Treatment: Drug: Tandospirone + Amlodipine; Drug: Tandospirone placebo + Amlodipine; Drug: Tandospirone + Amlodipine placebo; Drug: Tandospirone placebo + Amlodipine placebo

Detailed Description

In recent years, many studies have found that elevated blood pressure is associated with anxiety. It has been report that the incidence of hypertension with anxiety is 25%-54%. The studies have confirmed that anxiety can significantly reduce the antihypertensive effect. Therefore, anxiolytics can increase the antihypertensive effect in patients with hypertension and anxiety. However, there is currently no standard treatment for patients with hypertension and anxiety, and few clinical studies have focused on the treatment of these neglected patients. Improvement on hypertension through relieving anxiety and relief of anxiety through lowering hypertension are lack of clinical studies to prove. This study compares the antihypertensive effects between different treatment groups including antihypertensive drug, anxiolytic, and both, which provide a new clinical evidence for controlling blood pressure in patients with hypertension and anxiety.

• Study Type: Interventional
• Enrollment (Anticipated): 256
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
      • Beijing Friendship Hospital of Capital Medical University
    • Beijing, Beijing, China
      • Beijing Haidian Section of Peking University Third Hospital
    • Beijing, Beijing, China
      • Xuanwu Hospital of Capital Medical University
  • Chongqing
    • Chongqing, Chongqing, China
      • Yongchuan Hospital of Chongqing Medical University
  • Giangsu
    • Nanjing, Giangsu, China
      • Zhongda Hospital of Southeast University
  • Hebei
    • Tangshan, Hebei, China
      • Kailuan General Hospital
  • Shanxi
    • Taiyuan, Shanxi, China
      • The First Affiliated Hospital of Shanxi Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. An age of 60 - 80 years old;
2. Mild or moderate hypertension diagnosed in previous or at screening (office systolic blood pressure ≥ 140 mm Hg and ≤ 180 mm Hg, or diastolic blood pressure ≥ 90 mm Hg and ≤ 110 mm Hg, or both, on three readings on separate days when not taking any blood pressure drugs) ,and the blood pressure still meet the above criteria after the run-in period;
3. A total score ≥ 14 and ≤ 24 on the Hamilton Anxiety Scale (HAMA), except for panic disorder;
4. Informed consent signed.

Exclusion Criteria:

1. Secondary hypertension;
2. Office systolic blood pressure ≥ 180 mm Hg or diastolic blood pressure ≤ 110 mm Hg
3. Hypertension with target organ damage;
4. Cerebral hemorrhage, ischemic cerebral infarction, coronary artery disease, myocardial infarction, second-degree or third-degree atrioventricular block, sick sinus syndrome, atrial fibrillation, left ventricular hypertrophy, cardiac insufficiency (NYHA class Ⅱ-Ⅳ);
5. Diabetes and dyslipidemia;
6. Asthma, chronic obstructive pulmonary disease, bronchiectasis, and respiratory failure;
7. Inflammatory bowel disease, active gastritis, pancreatitis, partial or complete intestinal obstruction, and chronic diarrhea;
8. Acute or chronic hepatitis, hepatic insufficiency (ALT or AST is more than 2 times the upper limit of normal), and renal insufficiency (serum creatinine > 130 umol / L);
9. Uncontrolled thyroid diseases;
10. Severe or unstable central nervous system diseases;
11. Schizophrenia, bipolar disorder, severe intellectual disability, or severe cognitive impairment;
12. Having been diagnosed with alcohol or drug abuse within the past 1 year;
13. Presenting the risk of suicide, self-injury, and hurt others;
14. Having participated in other clinical studies within the past 3 months;
15. Having been treated with anxiolytics, antidepressants, antipsychotics within the past 4 weeks, or have contraindications to the study medications.
16. Breastfeeding, pregnancy, or a pregnancy plan during the study;
17. Other diseases which the responsible clinician judged that a change in current therapy would place the participant at risk.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1; Tandospirone + Amlodipine	Drug: Tandospirone + Amlodipine; The first group will receive a 30 mg dose of tandospirone one day( a 10 mg dose of tandospirone each time and three times a day) and a 5 mg dose of amlodipine one day(a 5 mg dose of amlodipine and one time a day).
Experimental: Group 2; Tandospirone placebo + Amlodipine	Drug: Tandospirone placebo + Amlodipine; The second group will receive a 30 mg dose of tandospirone placebo one day( a 10 mg dose of tandospirone placebo each time and three times a day) and a 5 mg dose of amlodipine one day(a 5 mg dose of amlodipine and one time a day).
Experimental: Group 3; Tandospirone + Amlodipine placebo	Drug: Tandospirone + Amlodipine placebo; The third group will receive a 30 mg dose of tandospirone one day( a 10 mg dose of tandospirone and three times a day) and a 5 mg dose of amlodipine placebo one day(a 5 mg dose of amlodipine placebo and one time a day).
Placebo Comparator: Group 4; Tandospirone placebo + Amlodipine placebo	Drug: Tandospirone placebo + Amlodipine placebo; The fourth group will receive a 30 mg dose of tandospirone placebo one day( a 10 mg dose of tandospirone placebo each time and three times a day) and a 5 mg dose of amlodipine placebo one day(a 5 mg dose of amlodipine placebo and one time a day).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Office systolic blood pressure and diastolic blood pressure		Change from Baseline Office systolic blood pressure and diastolic blood pressure at 4 weeks and 8 weeks
14-item Hamilton Anxiety Scale(HAMA)	HAMA-14 are rated on 5 grades ranging from 0(no symptom) to 4 (very severe). The total score ranges from 0 to 56. 29 or more on HAMA means severe anxiety disorders, 21 to 28 on HAMA means obvious anxiety disorders, 14 to 20 on HAMA means anxiety disorders, 8 to 13 on HAMA means suspicious anxiety disorders, 7 or less means no anxiety disorders.	Change from Baseline HAMA score at 4 weeks and 8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the proportion of patients who met blood pressure control goal( < 140/90mmHg)		Week 8
24-hour ambulatory blood pressure monitoring(ABPM)		Change from Baseline ABPM at 4 weeks and 8 weeks
the proportion of participants with an at least 50% reduction of HAMA score from baseline		Week 8
the proportion of participants showing 7 or less on HAMA		Week 8
20-item Self-Rating Anxiety Scale(SAS)	SAS-20 are rated on 4 grades ranging from 1(a little of the time) to 4(most of the time).The standard score ranges are 25-49 (normal range), 50-59 (mild anxiety), 60-69(moderate anxiety), and 70 or more(severe anxiety).	Change from Baseline SAS score at 4 weeks and 8 weeks
heart rate variability(HRV)		Change from Baseline HRV at 4 weeks and 8 weeks
17-item Hamilton Depression Rating Scale(HAMD)	HAMD-17 are rated on 5 grades ranging from 0 (no symptom) to 4 (very severe). 7 or less on HAMD means no depression, 7 to 17 on HAMD means mild depression, 18 to 23 on HAMD means moderate depression, and 24 or more on HAMD means severe depression.	Change from Baseline HAMD score at 4 weeks and 8 weeks
Clinical Global Impression-Improvement(CGI-I)		Change from Baseline CGI-I score at 4 weeks and 8 weeks
Quality of Life Enjoyment and Satisfaction Questionnaire(Q-LES-Q)	Q-LES-Q are rated on 5 grades ranging from 1 to 5 points.	Change from Baseline Q-LES-Q score at 4 weeks and 8 weeks

Collaborators and Investigators

• Sponsor: Chongqing Medical University

Publications and helpful links

General Publications

• Bhattacharya R, Shen C, Sambamoorthi U. Excess risk of chronic physical conditions associated with depression and anxiety. BMC Psychiatry. 2014 Jan 16;14:10. doi: 10.1186/1471-244X-14-10.
• Pan Y, Cai W, Cheng Q, Dong W, An T, Yan J. Association between anxiety and hypertension: a systematic review and meta-analysis of epidemiological studies. Neuropsychiatr Dis Treat. 2015 Apr 22;11:1121-30. doi: 10.2147/NDT.S77710. eCollection 2015.
• Byrd JB, Brook RD. Anxiety in the "age of hypertension". Curr Hypertens Rep. 2014 Oct;16(10):486. doi: 10.1007/s11906-014-0486-0.
• Kretchy IA, Owusu-Daaku FT, Danquah SA. Mental health in hypertension: assessing symptoms of anxiety, depression and stress on anti-hypertensive medication adherence. Int J Ment Health Syst. 2014 Jun 21;8:25. doi: 10.1186/1752-4458-8-25. eCollection 2014.

Study record dates

Study Major Dates

• Study Start (Anticipated): February 1, 2019
• Primary Completion (Anticipated): February 1, 2020
• Study Completion (Anticipated): July 1, 2020

Study Registration Dates

• First Submitted: September 6, 2018
• First Submitted That Met QC Criteria: September 10, 2018
• First Posted (Actual): September 12, 2018

Study Record Updates

• Last Update Posted (Actual): December 4, 2018
• Last Update Submitted That Met QC Criteria: November 30, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: Hypertension; Anxiety; Amlodipine; Tandospirone
• Additional Relevant MeSH Terms: Mental Disorders; Cardiovascular Diseases; Vascular Diseases; Hypertension; Anxiety Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Central Nervous System Depressants; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Serotonin Agents; Serotonin Receptor Agonists; Anti-Anxiety Agents; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Amlodipine; Tandospirone
• Other Study ID Numbers: CES-TAHA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Any public report on the results of this study will not disclose personal information of the participants.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No