Clonidine + Hydrochlorothiazide for High Blood Pressure

(SELECT Trial)

Recruiting at 1 trial location

Overseen By Gary L Pierce, PhD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Iowa

Must not be taking: Aspirin, NSAIDs, SSRIs, others

Disqualifiers: Cardiovascular, Pulmonary, Diabetes, Cancer, others

Compensation: Varies

Number of Visits: 4

Duration: 4 weeks

78 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

If you are on antihypertensive medications, you will need to stop taking them for a one-week period before the second visit. Other medications like aspirin, NSAIDs, vitamins, and certain supplements must be stopped at least one week before and during the study.

What data supports the effectiveness of the drug Clonidine for high blood pressure?

Clonidine is effective in reducing blood pressure, especially when used with a diuretic, and is well-tolerated by most patients. It has been shown to significantly lower blood pressure in patients with mild to moderate hypertension, and its effectiveness is enhanced when combined with a diuretic. ^{1 2 3 4 5}

Is the combination of Clonidine and Hydrochlorothiazide safe for treating high blood pressure?

Clonidine, often used with a diuretic like Hydrochlorothiazide, is generally well-tolerated with serious side effects being uncommon. Common side effects include sedation and dry mouth, which can be managed by adjusting the dose. The combination has been shown to effectively lower blood pressure with a good safety profile. ^{1 5 6 7 8}

What makes the drug combination of Clonidine and Hydrochlorothiazide unique for treating high blood pressure?

The combination of Clonidine and Hydrochlorothiazide is unique because Clonidine, an alpha-adrenergic receptor agonist, reduces blood pressure by decreasing sympathetic nerve signals, while Hydrochlorothiazide is a diuretic that helps remove excess fluid from the body. This dual action can enhance the antihypertensive effect, making it effective for patients who may not respond well to single-drug treatments. ^{5 7 8 9 10}

What is the purpose of this trial?

Stiffening of your blood vessels, particularly the large vessels from your heart (called the aorta and carotids) you age contributes to the development of cardiovascular disease (CVD) such as heart attack and stroke. Nerve activity from your brain to your body also increases with advancing age but it is unknown if this nerve activity contributes directly to the stiffening on your blood vessels in older adults in addition to high blood pressure. Therefore, successful completion of the proposed aims will have a significant clinical impact by identifying if nerve activity from your brain could be a novel target for therapies that would lower stiffness of the aorta and carotid arteries in older adults.

Research Team

Gary Pierce, PhD

Principal Investigator

University of Iowa

Eligibility Criteria

This trial is for non-smoking adults aged 60-85 with untreated or treated stage 1 or 2 isolated systolic hypertension. Participants must be clinically healthy and not on certain medications like aspirin, NSAIDs, vitamins, or supplements. Women should be postmenopausal without hormone therapy. Those with a history of serious health conditions such as heart disease, diabetes, cancer are excluded.

Inclusion Criteria

I can stop my blood pressure medication for a week and have a systolic BP under 160 mmHg.

I am between 60 and 85 years old.

Non-smoking

Exclusion Criteria

I am a woman who has been postmenopausal for at least 6 months and am not on hormone replacement therapy.

My blood pressure is not between 130/90 and 160/90 mmHg without medication.

I can stop taking aspirin, NSAIDs, vitamins, herbal supplements, and omega-3 for a week before and during the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Clonidine, Hydrochlorothiazide, or a placebo for 4 weeks

4 weeks

Baseline and after 4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Clonidine
• Hydrochlorothiazide
• Placebo

Trial Overview The study tests if reducing nerve activity from the brain can decrease stiffness in large arteries to prevent cardiovascular diseases. It compares the effects of Clonidine (a blood pressure medication) and Hydrochlorothiazide (a diuretic) against a placebo in older adults with high systolic blood pressure.

Participant Groups

Group I: Clonidine Experimental Treatment 1 Intervention

0.2 mg/day oral

Group II: Hydrochlorothiazide Active Control 1 Intervention

37.5 mg/day oral

Group III: Placebo Placebo Group 1 Intervention

Placebo

Clonidine is already approved in United States, European Union for the following indications:

Approved in United States as Catapres for:

• Hypertension
• ADHD
• Severe cancer pain
• Withdrawal symptoms from various substances
• Diagnosis of pheochromocytoma
• Prevention of migraines

Approved in European Union as Catapres for:

• Hypertension
• ADHD
• Severe cancer pain
• Withdrawal symptoms from various substances
• Diagnosis of pheochromocytoma
• Prevention of migraines

Who Is Running the Clinical Trial?

University of Iowa

Lead Sponsor

Trials

486

Recruited

934,000+

Findings from Research

A compounded oral clonidine hydrochloride powder (0.2 mg/g) maintained its stability and quality for 120 days under controlled storage conditions, ensuring consistent dosing for pediatric patients.

No degradation products were detected, and the clonidine content remained within the acceptable range (90.0% to 110.0% of initial content), indicating that the compounded formulation is safe and effective for use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stability of clonidine hydrochloride in an oral powder form compounded for pediatric patients in Japan. Saito, J., Hanawa, T., Matsumoto, T., et al.[2021]

Clonidine (Catapres-TTS) was effective in significantly reducing blood pressure in 11 out of 25 patients with mild to moderate hypertension during the first four weeks of treatment, but did not show significant effects in patients with more severe hypertension.

While some patients experienced localized contact dermatitis leading to discontinuation of the patch, other side effects like drowsiness and dry mouth were less common compared to oral clonidine, making Catapres-TTS a potentially better option for those who have trouble with the oral form.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient acceptance of transdermal clonidine. A retrospective review of 25 patients. Chen, SW., Vidt, DG.[2019]

In a study of 62 mild hypertensive patients, transdermal clonidine was effective in reducing blood pressure, achieving satisfactory control in 85% of participants after 3 months of treatment.

The efficacy of transdermal clonidine was comparable to that of previous treatments (diuretics and beta-blockers), with minimal systemic side effects, although some patients experienced local allergic reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transdermal clonidine (Catapres-TTS) monotherapy in the management of mild hypertension in general practice. Lewis, GR.[2014]

Clonidine hydrochloride is an effective antihypertensive medication that works primarily in the central nervous system and is particularly beneficial for long-term treatment of moderately severe hypertension when combined with a diuretic.

While clonidine is comparable to methyldopa in terms of efficacy, it may have a higher frequency of side effects, with a notable risk of rebound hypertension if the medication is stopped too quickly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of clonidine hydrochloride (Catapres). A new antihypertensive agent. Kosman, ME.[2016]

Clonidine hydrochloride is an effective antihypertensive medication that reduces blood pressure and heart rate without significantly affecting cardiac output or renal function, making it suitable for patients with various comorbidities.

The drug is well-tolerated by over 93% of patients, with common side effects like sedation and dry mouth that can be managed by adjusting the dosage, highlighting its safety profile in long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clonidine hydrochloride. Houston, MC.[2019]

In a study involving 26 patients with mild to moderate hypertension, both lofexidine and clonidine significantly reduced blood pressure compared to placebo, indicating their efficacy in managing hypertension.

Lofexidine was found to have a lower incidence of adverse effects compared to clonidine, suggesting it may be a safer alternative for patients requiring blood pressure control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative efficacy and safety of lofexidine and clonidine in mild to moderately severe systemic hypertension. Lopez, LM., Mehta, JL.[2019]

In a study of 41 hypertensive patients, the new anti-hypertensive agent dimapres effectively lowered blood pressure to normal levels, demonstrating good tolerance among patients regardless of their previous treatments.

Dimapres not only controlled blood pressure but also improved exercise tolerance, indicating it reduces the body's reactivity to stressors, which is beneficial for hypertensive patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Therapy of hypertension with dimapres. Studies on the effect of the anti-hypertensive drug dimapres in newly adjusted and pretreated hypertensive patients]. Engelking, H.[2013]

In a study involving 14 patients, the antihypertensive effects of a clonidine-chlorthalidone combination taken as a single daily dose at bedtime were found to be similar to those taken in twice-daily doses.

There were no significant differences in blood pressure control or side effects between the two dosing regimens, suggesting that either method is equally effective and safe for managing hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clonidine-chlorthalidone combination once and twice daily in essential hypertension. Noveck, RJ., McMahon, FG., Jain, AK., et al.[2019]

In a study of 30 hypertensive subjects, both clonidine and tiamenidine effectively lowered blood pressure and catecholamine levels, but withdrawal symptoms were infrequent and similar for both medications.

Upon withdrawal, some subjects experienced a significant rise in blood pressure, which correlated with increased norepinephrine levels, indicating that the rebound effect is linked to the loss of drug-induced catecholamine suppression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Withdrawal phenomena in subjects with essential hypertension on clonidine or tiamenidine. Hamilton, BP., Mersey, JH., Hamilton, J., et al.[2019]

A combination of 150 mcg clonidine and 2.5 mg cyclothiazide was tested in at least 20 patients over 4 weeks and showed promising results for long-term hypertension treatment with fewer side effects compared to using the drugs individually.

This combination effectively lowered blood pressure in patients with mild to moderate hypertension, as confirmed by daily blood pressure measurements and ergometric tests.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical trial of a combination preparation of clonidine and cyclothiazide (author's transl)]. Wimmer, PP.[2013]

References

1. England pubmed.ncbi.nlm.nih.gov

Stability of clonidine hydrochloride in an oral powder form compounded for pediatric patients in Japan. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Patient acceptance of transdermal clonidine. A retrospective review of 25 patients. [2019]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Transdermal clonidine (Catapres-TTS) monotherapy in the management of mild hypertension in general practice. [2014]

4. United States pubmed.ncbi.nlm.nih.gov

Evaluation of clonidine hydrochloride (Catapres). A new antihypertensive agent. [2016]

5. United States pubmed.ncbi.nlm.nih.gov

Clonidine hydrochloride. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Comparative efficacy and safety of lofexidine and clonidine in mild to moderately severe systemic hypertension. [2019]

7. Germany pubmed.ncbi.nlm.nih.gov

[Therapy of hypertension with dimapres. Studies on the effect of the anti-hypertensive drug dimapres in newly adjusted and pretreated hypertensive patients]. [2013]

8. United States pubmed.ncbi.nlm.nih.gov

Clonidine-chlorthalidone combination once and twice daily in essential hypertension. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

Withdrawal phenomena in subjects with essential hypertension on clonidine or tiamenidine. [2019]

10. Germany pubmed.ncbi.nlm.nih.gov

[Clinical trial of a combination preparation of clonidine and cyclothiazide (author's transl)]. [2013]