The Influence of Hypotensive Drugs on Mineral Status in Experimental and Clinical Studies

Study Overview
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Brief Summary
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The aim of the study was to evaluate the effects of hypotensive treatment combined with a higher zinc supply in the diet and supplements on the mineral status and selected biochemical parameters of newly diagnosed hypertensive patients on monotherapy.

Detailed Description
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The study was designed as a prospective randomized trial and was performed in three stages. In the first stage, primary hypertension was diagnosed and antihypertensive monotherapy was implemented. In the second stage, patients underwent antihypertensive monotherapy lasting three months. The subjects received diuretics; calcium antagonists (Ca-antagonists); angiotensin-converting-enzyme inhibitors (ACE-Is); angiotensin II receptor antagonists (ARBs); or β-blockers. After three months of monotherapy, patients were divided using a randomization list into three equal groups: C (control group), D (diet group) and S (supplementation group). In the third stage, which lasted 30 days, subjects from all groups received the same antihypertensive drug as in the second stage and either an optimal-mineral-content diet (group D), zinc supplementation (group S), or continued drug use with no change in diet and no mineral supplementation (group C). Patients from group D received an optimal-mineral-content properly balanced diet enriched in food with high zinc content prepared individually for each patient by a qualified dietician. Patients from group S received zinc supplementation as one capsule containing 15 mg of Zn taken orally once a day in the morning, two hours after antihypertensive drug administration with no change in diet, through all 30 days of the third stage of the trial. During the study, patients were asked to not use dietary supplements and not to change their lifestyle or level of physical activity. On the last day of each stage of the study, blood, urine, and hair samples were collected from the subjects, and blood pressure and anthropometric parameters were measured.

Official Title
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The Influence of Hypotensive Drugs on Zinc, Copper and Iron Status in Experimental and Clinical Studies.

Conditions
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Nutritional Disorder, Hypertension, Mineral Deficiency

Intervention / Treatment
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* Dietary Supplement: group/arm C (control group)
* Dietary Supplement: group/arm D (diet group)
* Dietary Supplement: group/arm S (supplementation group)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: informed written consent; age 18-65 years; primary hypertension; beginning monotherapy with an antihypertensive drug; stable body weight (less than 3 kg self-reported change during the three months prior to enrollment). Exclusion Criteria: any secondary form of hypertension; the use of mineral supplements within the three months prior to enrollment; lipid disorders requiring treatment in the three months prior to the trial; a history of ischemic heart disease, stroke, congestive heart failure, clinically significant arrhythmia or conduction disorders, peripheral artery or vein disease, diabetes mellitus, abnormal renal, liver or thyroid gland function, clinically significant chronic or acute inflammatory process within the respiratory, genitourinary, or digestive tract, or in the oral cavity, larynx, pharynx, or in the paranasal sinuses, or connective tissue diseases, arthritis, or malignancy; infection in the month prior to enrollment, having an pacemaker implanted; alcohol, nicotine or drug abuse; mental disorders; pregnancy, childbirth or lactation at enrollment or in the three months prior to enrollment; or any other condition that, in the opinion of investigators, would make participation in the study not in the best interest of the subject, or could prevent, limit, or confound the efficacy of the study.

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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Accepts Healthy Volunteers

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
Interventional Model Description: Three stages of the study: stage 1- diagnosis of primary hypertension stage 2 (lasting 3 months) - antihypertensive monotherapy in all subjects stage 3 (lasting 30 days) - 3 groups (3 arms): group/arm C (control group), group/arm D (diet group) and group/arm S (supplementation group).
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: group/arm C (control group)<br>Group C in the third stage (30 days) continued drug use with no change in diet and no mineral supplementation. | Dietary Supplement: group/arm C (control group)<br>* Group C in the third stage (30 days) continued drug use with no change in diet and no mineral supplementation.<br>|
| Active Comparator: group/arm D (diet group)<br>Group D in the third stage (30 days) received an optimal-mineral-content properly balanced diet enriched in food with high zinc content. | Dietary Supplement: group/arm D (diet group)<br>* Group D in the third stage (30 days) received an optimal-mineral-content properly balanced diet enriched in food with high zinc content.<br>|
| Active Comparator: group/arm S (supplementation group)<br>Group S in the third stage (30 days) received zinc supplementation as one capsule containing 15 mg of Zn taken orally once a day in the morning, two hours after antihypertensive drug administration with no change in diet. | Dietary Supplement: group/arm S (supplementation group)<br>* Group S in the third stage (30 days) received zinc supplementation as one capsule containing 15 mg of Zn taken orally once a day in the morning, two hours after antihypertensive drug administration with no change in diet.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum zinc- stage I | Serum zinc concentration in stage I of the trial | At baseline | 
| Serum zinc- stage II | Serum zinc concentration in stage II of the trial | After 3 months | 
| Serum zinc- stage III | Serum zinc concentration in stage III of the trial | After 3 months and 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body mass- stage I | Body mass in stage I | At baseline | 
| Body mass- stage II | Body mass in stage II | After 3 months | 
| Body mass- stage III | Body mass in stage III | After 3 months and 30 days | 
| Body height- stage I | Body height in stage I | At baseline | 
| Body height- stage II | Body height in stage II | After 3 months | 
| Body height- stage III | Body height in stage III | After 3 months and 30 days | 
| Blood pressure- stage I | Blood pressure in stage I | At baseline | 
| Blood pressure- stage II | Blood pressure in stage II | After 3 months | 
| Blood pressure- stage III | Blood pressure in stage III | After 3 months and 30 days | 
| Erythrocytes zinc- stage I | Zinc concentration in erythrocytes in stage I | At baseline | 
| Erythrocytes zinc- stage II | Zinc concentration in erythrocytes in stage II | After 3 months | 
| Erythrocytes zinc- stage III | Zinc concentration in erythrocytes in stage III | After 3 months and 30 days | 
| Urine zinc- stage I | Zinc concentration in urine in stage I | At baseline | 
| Urine zinc- stage II | Zinc concentration in urine in stage II | After 3 months | 
| Urine zinc- stage III | Zinc concentration in urine in stage III | After 3 months and 30 days | 
| Hair zinc- stage I | Zinc content in hair in stage I | At baseline | 
| Hair zinc- stage II | Zinc content in hair in stage II | After 3 months | 
| Hair zinc- stage III | Zinc content in hair in stage III | After 3 months and 30 days | 
| Serum iron- stage I | Iron concentration in serum in stage I | At baseline | 
| Serum iron- stage II | Iron concentration in serum in stage II | After 3 months | 
| Serum iron- stage III | Iron concentration in serum in stage III | After 3 months and 30 days | 
| Erythrocytes iron- stage I | Iron concentration in erythrocytes in stage I | At baseline | 
| Erythrocytes iron- stage II | Iron concentration in erythrocytes in stage II | After 3 months | 
| Erythrocytes iron- stage III | Iron concentration in erythrocytes in stage III | After 3 months and 30 days | 
| Urine iron- stage I | Iron concentration in urine in stage I | At baseline | 
| Urine iron- stage II | Iron concentration in urine in stage II | After 3 months | 
| Urine iron- stage III | Iron concentration in urine in stage III | After 3 months and 30 days | 
| Hair iron- stage I | Iron content in hair in stage I | At baseline | 
| Hair iron- stage II | Iron content in hair in stage II | After 3 months | 
| Hair iron- stage III | Iron content in hair in stage III | After 3 months and 30 days | 
| Serum copper- stage I | Serum copper concentration in stage I | At baseline | 
| Serum copper- stage II | Serum copper concentration in stage II | After 3 months | 
| Serum copper- stage III | Serum copper concentration in stage III | After 3 months and 30 days | 
| Erythrocytes copper- stage I | Erythrocytes copper concentration in stage I | At baseline | 
| Erythrocytes copper- stage II | Erythrocytes copper concentration in stage II | After 3 months | 
| Erythrocytes copper- stage III | Erythrocytes copper concentration in stage III | After 3 months and 30 days | 
| Urine copper- stage I | Urine copper concentration in stage I | At baseline | 
| Urine copper- stage II | Urine copper concentration in stage II | After 3 months | 
| Urine copper- stage III | Urine copper concentration in stage III | After 3 months and 30 days | 
| Hair copper- stage I | Hair copper content in stage I | At baseline | 
| Hair copper- stage II | Hair copper content in stage II | After 3 months | 
| Hair copper- stage III | Hair copper content in stage III | After 3 months and 30 days | 
| Glucose- stage I | Glucose serum concentration in stage I | At baseline | 
| Glucose- stage II | Glucose serum concentration in stage II | After 3 months | 
| Glucose- stage III | Glucose serum concentration in stage III | After 3 months and 30 days | 
| C-reactive protein- stage I | C-reactive protein serum concentration in stage I | At baseline | 
| C-reactive protein- stage II | C-reactive protein serum concentration in stage II | After 3 months | 
| C-reactive protein- stage III | C-reactive protein serum concentration in stage III | After 3 months and 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hypertension,, zinc, zinc supplementation, antihypertensive monotherapy, mineral status