Clonidine + Hydrochlorothiazide for High Blood Pressure

(SELECT Trial)

No longer 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how two medications, Clonidine (used to treat high blood pressure) and Hydrochlorothiazide (a diuretic for high blood pressure), might reduce stiffness in large blood vessels in older adults. Researchers aim to determine if nerve activity from the brain affects this stiffness, which can lead to heart disease and strokes. Participants will receive either one of the medications or a placebo to compare effects. The study seeks non-smoking adults aged 60-85 with untreated or treated stage 1 or 2 isolated systolic hypertension, who are otherwise clinically healthy. As an Early Phase 1 trial, this research focuses on understanding how these treatments work in people, offering participants a chance to contribute to groundbreaking medical insights.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that clonidine helps lower blood pressure by relaxing the arteries and improving blood flow to the heart. Some people using clonidine have experienced lower heart rates and blood pressure, so monitoring these is important. Clonidine has been approved for other uses, indicating its safety has been studied in people before. However, stopping clonidine suddenly can cause serious side effects like nervousness or agitation.

Studies indicate that hydrochlorothiazide is also commonly used to treat high blood pressure. It helps control blood pressure, reducing the risk of heart attacks. Some people may feel dizzy, especially if they drink alcohol while taking it. Long-term use of hydrochlorothiazide might increase the risk of skin cancer.

Both treatments have been used in other approved situations, suggesting a known safety profile. However, since this trial is in its early stages, the full safety for the specific condition being studied is still being explored. Participants in early trials help researchers better understand safety and potential side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining Clonidine and Hydrochlorothiazide for high blood pressure because this approach targets multiple pathways to lower blood pressure more effectively. Unlike standard treatments like ACE inhibitors or beta-blockers that focus on one mechanism, Clonidine works by reducing heart rate and relaxing blood vessels, while Hydrochlorothiazide helps the body get rid of excess salt and water. This dual-action strategy might offer better control of blood pressure, potentially reducing the risk of complications like heart attacks or strokes.

What evidence suggests that this trial's treatments could be effective for high blood pressure?

In this trial, participants will receive clonidine, hydrochlorothiazide, or a placebo. Research has shown that clonidine effectively lowers blood pressure quickly, which is useful when rapid reduction is necessary. Controlling blood pressure is crucial for preventing heart attacks and strokes. Hydrochlorothiazide also lowers blood pressure by helping blood vessels relax and widen. Although commonly used, evidence does not show that it reduces heart attacks or strokes on its own. Both treatments help manage high blood pressure, potentially reducing the stiffening of large blood vessels over time. ^{4 6 7 8 9}

Who Is on the Research Team?

Gary Pierce, PhD

Principal Investigator

University of Iowa

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

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]

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]

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]

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]

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]

Citations

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Blood pressure lowering efficacy of clonidine for primary ... Clonidine was first used as a nasal decongestant and was found serendipitously to have blood pressure lowering effects.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9931607/

Comparing outcomes of clonidine and captopril in patients ... Based on our results, in the patients with hypertensive urgency, using clonidine was better than captopril, because using clonidine had faster effect than ...

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Kapvay - accessdata.fda.gov In adults with hypertension, sudden cessation of treatment with immediate-release clonidine has, in some cases, resulted in symptoms such as nervousness, ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT01761916?term=CLONIDINE&viewType=Table&rank=1

Clonidine Versus Captopril for Treatment of Postpartum ... What is not known yet is how long clonidine reduces high blood pressure and how long to leave stabilized compared to the use of captopril. There are no reports ...

5. hhs.texas.gov hhs.texas.gov/sites/default/files/documents/clonidine-er-kapvay-monograph.pdf

Clonidine Hydrochloride ER (Kapvay®) Effect on Blood Pressure and Heart Rate: In patients that completed 5 weeks of treatment in a controlled, fixed-dose monotherapy study in ...

6. mayoclinic.org mayoclinic.org/drugs-supplements/clonidine-oral-route/description/drg-20063252

Clonidine (oral route) - Side effects & dosage Your blood pressure may become worse when the medicine is stopped suddenly, which can cause serious side effects (eg, agitation, nervousness, ...

7. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK459124/

Clonidine - StatPearls - NCBI Bookshelf Clonidine is an antihypertensive drug that lowers blood pressure and heart rate by relaxing the arteries and increasing the blood supply to the heart.

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2020/022331s021lbl.pdf

KAPVAY® (clonidine hydrochloride) extended-release tablets Treatment with KAPVAY can cause dose-related decreases in blood pressure and heart rate [see Adverse Reactions (6.1)]. Measure heart rate and blood pressure ...

9. drugs.com drugs.com/clonidine.html

Clonidine: Uses, Dosage, Side Effects, Warnings To make sure clonidine is safe for you, tell your doctor if you have: heart disease or severe coronary artery disease;. a heart rhythm disorder, ...