Study 1: Effect of Minocycline Treatment on Drug-Resistant Hypertensive Patients
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|ClinicalTrials.gov Identifier: NCT02133872|
Recruitment Status : Recruiting
First Posted : May 8, 2014
Last Update Posted : August 31, 2018
Hypertension (HTN) is the single most prevalent risk factor for cardiovascular disease, diabetes, obesity and metabolic syndrome. Recent American Heart Association (AHA) statistics indicate that one-third of all adults in the United States of America suffer from HTN. Despite advances in life style modification and multi-drug therapies, 20-30% of all hypertensive patients remain resistant.
These individuals exhibit autonomic dysregulation due to elevated sympathetic activity and norepinephrine spillover, and low parasympathetic activity. It is generally accepted that this uncontrolled, resistant HTN is primarily "neurogenic" in origin, involving over activity of the sympathetic nervous system that initiates and sustains HTN. A surgical approach such as the recently developed "Simplicity Catheter" assisted renal denervation remains one of the few options available to these patients. Thus, a mechanism-based breakthrough is imperative to develop novel strategies to prevent and perhaps eventually cure neurogenic hypertension (NH). This study is designed to evaluate a low and high dose of minocycline to test the hypothesis that minocycline treatment would produce antihypertensive effects in drug-resistant neurogenic hypertensive individuals. Minocycline has been selected because of its demonstrated effects on inhibiting microglial activation and its ability to penetrate the blood brain barrier. There is no other compound available that is safer and displays specificity better than Minocycline in inhibiting microglial activation. Thus, the potential therapeutic benefits of this inexpensive, well tolerated, already FDA-approved drug that has minimal side effects would be enormous.
|Condition or disease||Intervention/treatment||Phase|
|Hypertension||Drug: Minocycline 100mg Group Drug: Minocycline 200mg Group||Phase 1|
One hundred seventy-five (175) subjects who will be randomized to receive either Minocycline 100 mg or 200 mg b.i.d. (twice a day). At baseline, subjects will undergo blood tests (lipid panel, high sensitivity-C reactive protein, high sensitivity troponin, glucose, metabolic profile, lipid panel, Cystatin C, albumin and flow cytometry). Peripheral blood mononuclear cells will be isolated and used to generate human induced pluripotent stem cells (iPSCs) which will be used for further mechanism studies.
In addition to blood collection, a physical exam will be conducted and office systolic blood pressure (BP), diastolic blood pressure (DBP) and pulse pressure (PP) will be recorded. Patients will also be fitted with an ambulatory blood pressure monitor (ABPM) system. Patients will wear the ABPM for 24 hours at which point they will mail the monitor back to research personnel. A week later, a second ABPM baseline reading will be conducted as patients will return to the clinic to be fitted again with the ABPM. At this visit, the study drug will be dispensed and patients will be instructed to start the study medication after completing the 24- hour ABPM monitoring period. After this visit, patients will be asked to return every month till the end of the study at 6 months.
Monthly visits (1, 2, 3, 4, 5 and 6 month visits), will include a brief physical examination and an assessment of medication compliance and tolerance. One tablespoon of blood will be drawn for flow cytometry analysis and iPSCs isolation at the baseline, 3 and 6 month visit only. Study drug will be dispensed and measurement of SBP, DBP, PP and other vital signs will also be completed. Office BP readings will be taken in a seated position after 5 minutes of rest according to Joint National Committee VII Guidelines. At baseline, BP will be measured at each arm, and the arm with the higher BP will be used for all subsequent readings. Averages of the triplicate measures will be calculated and used for analysis. At baseline and each followup visit, patients will be asked to wear the ABPM for 24 hours. Subjects will mail the cuff back to research personnel when completed. ABPM will be performed using an oscillometric Spacelabs 90207 monitor (Spacelabs Healthcare, Issaqua, WA) with readings taken every 30 minutes in daytime and every 60 minutes at nighttime. ABPM readings will be averaged for, daytime (8 AM to 5 PM), and nighttime (10 PM to 7 AM). Patients will be assessed while adhering to their usual diurnal activity and nocturnal sleep routine. The antihypertensive drugs, and their doses, used at each visit will be recorded on standardized forms along with any reports of adverse experiences known to occur with the drugs used (e.g. lightheadedness, dizziness, syncope, etc.).
Only at the final visit, the same blood tests at baseline will be repeated. When the patients complete the 6 months of treatment, come in for their final visit, and return the ABPM monitor, their participation in the trial will be considered as complete.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||175 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Angiotensin and Neuroimmune Activation in Hypertension|
|Study Start Date :||October 2014|
|Estimated Primary Completion Date :||May 2019|
|Estimated Study Completion Date :||May 2019|
Active Comparator: Minocycline 100mg Group
Subjects will be randomized to receive Minocycline 100mg.
Drug: Minocycline 100mg Group
Subjects will be randomized to receive Minocycline 100mg
Active Comparator: Minocycline 200mg Group
Subjects will be randomized to receive Minocycline 200mg
Drug: Minocycline 200mg Group
Subjects will be randomized to receive Minocycline 200mg.
- Reduction in High Blood Pressure [ Time Frame: 52 weeks ]Reduction in anti-hypertensive medications
- Renal function changes [ Time Frame: 52 weeks ]Lab results
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02133872
|Contact: Dana Leach, DNPfirstname.lastname@example.org|
|Contact: Sarah Long, RNemail@example.com|
|United States, Florida|
|UF Health Cardiovascular Clinic||Recruiting|
|Gainesville, Florida, United States, 32610|
|Contact: Dana Leach, DNP 352-273-8933 firstname.lastname@example.org|
|Sub-Investigator: Mohan Raizada, PhD|
|Principal Investigator:||Carl Pepine, MD||University of Florida|