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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Hypertension, Anxiety

Intervention / Treatment
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* Drug: Tandospirone + Amlodipine
* Drug: Tandospirone placebo + Amlodipine
* Drug: Tandospirone + Amlodipine placebo
* Drug: Tandospirone placebo + Amlodipine placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: An age of 60 - 80 years old; 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; A total score ≥ 14 and ≤ 24 on the Hamilton Anxiety Scale (HAMA), except for panic disorder; Informed consent signed. Exclusion Criteria: Secondary hypertension; Office systolic blood pressure ≥ 180 mm Hg or diastolic blood pressure ≤ 110 mm Hg Hypertension with target organ damage; 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); Diabetes and dyslipidemia; Asthma, chronic obstructive pulmonary disease, bronchiectasis, and respiratory failure; Inflammatory bowel disease, active gastritis, pancreatitis, partial or complete intestinal obstruction, and chronic diarrhea; 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); Uncontrolled thyroid diseases; Severe or unstable central nervous system diseases; Schizophrenia, bipolar disorder, severe intellectual disability, or severe cognitive impairment; Having been diagnosed with alcohol or drug abuse within the past 1 year; Presenting the risk of suicide, self-injury, and hurt others; Having participated in other clinical studies within the past 3 months; Having been treated with anxiolytics, antidepressants, antipsychotics within the past 4 weeks, or have contraindications to the study medications. Breastfeeding, pregnancy, or a pregnancy plan during the study; Other diseases which the responsible clinician judged that a change in current therapy would place the participant at risk.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>Tandospirone + Amlodipine | Drug: Tandospirone + Amlodipine<br>* 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).<br>|
| Experimental: Group 2<br>Tandospirone placebo + Amlodipine | Drug: Tandospirone placebo + Amlodipine<br>* 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).<br>|
| Experimental: Group 3<br>Tandospirone + Amlodipine placebo | Drug: Tandospirone + Amlodipine placebo<br>* 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).<br>|
| Placebo Comparator: Group 4<br>Tandospirone placebo + Amlodipine placebo | Drug: Tandospirone placebo + Amlodipine placebo<br>* 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).<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypertension, Anxiety, Tandospirone, Amlodipine