HypertensionPhase 2NCT02133872
Study 1: Effect of Minocycline Treatment on Drug-Resistant Hypertensive Patients
A Phase 2 study testing Minocycline 50mg/d, Minocycline 100mg/d and Minocycline 200mg/d in people with Hypertension, run by University of Florida at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Hypertension
- What is being tested?
- Minocycline 50mg/d, Minocycline 100mg/d and Minocycline 200mg/d
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2014to 1 Nov 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Greater than 18 and less than 86 years of age;
- On stable medication regimen
- Full-tolerated doses of 3 or more antihypertensive medications of different classes, one of which must be a diuretic (with no changes for a minimum of two months prior to screening) that is expected to be maintained without changes for at least 3 months.
- The individual agrees to have all study procedures performed
- Willing to provide written consent
Who cannot join
- eGFR of < 45mL/min/1.73m2, using the MDRD calculation.
- More than one in-patient hospitalization for an antihypertensive crisis within the year.
- More than one episode(s) of orthostatic hypotension (reduction of SBP of ≥ 20mmHg of diastolic blood pressure (DBP) of ≥ 10mmHg within 3 minutes of standing).
- Known hypersensitivity or contraindication to Minocycline or other tetracycline.
- Evidence of alcoholism or drug abuse;
- Concurrent severe disease (such as neoplasm or HIV positive or AIDS).
- Women of childbearing potential
Trial locations and contacts
1 site in 1 country.
United States1 site
UF Health Cardiovascular Clinic
Gainesville, Florida, 32610
About this study
Official title: Angiotensin and Neuroimmune Activation in Hypertension
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.
Read the detailed description
Open-label design of dose titration for each participant beginning at 50 mg/day of minocycline, escalating to 100 mg/day and 200 mg/day if the primary outcome measure of ambulatory blood pressure monitor (ABPM) =/> to 5 mmHg decrease in mean daytime SBP was not achieved. If patients responded, participation was completed. This revised protocol was resubmitted to the IRB and approved on 1/6/16. An interim analysis was planned after 40 patients completed the revised protocol.
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 be fitted with an ABPM system. Patients will wear the ABPM for 24 hours at which point they will mail the monitor back to research personnel. 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, selected cytokines, markers of gut permeability including zonulin, 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 and nighttime. 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.).
If patients respond to treatment, by protocol defined drop in daytime ABPM and/or the need for down titration of hypertensive therapy they will be considered a responder, complete the final visit and complete study participation. At the final visit, the same blood tests at baseline will be repeated. When the patients complete the 6 months of treatment or are considered a responder at a lower dose, they will come in for their final visit, and return the ABPM monitor, their participation in the trial will be considered as complete.
- Conditions
- Hypertension
- Being tested
- Minocycline 50mg/d, Minocycline 100mg/d, Minocycline 200mg/d
- Keywords
- Resistent Hypertension
- Medical subject headings
- Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Minocycline 50mg/dDrug
Subjects will receive minocycline 50mg if no mean daytime ABPM SBP decline =/> 5mm Hg; subjects will receive minocycline 100mg, if no mean daytime ABPM SBP decline =/> 5mm Hg BP subjects will receive minocycline 200 mg.
Minocycline 100mg/dDrug
Subjects will receive minocycline 50mg if no mean daytime ABPM SBP decline =/> 5mm Hg; subjects will receive minocycline 100mg, if no mean daytime ABPM SBP decline =/> 5mm Hg BP subjects will receive minocycline 200 mg.
Minocycline 200mg/dDevice
Subjects will receive minocycline 50mg if no mean daytime ABPM SBP decline =/> 5mm Hg; subjects will receive minocycline 100mg, if no mean daytime ABPM SBP decline =/> 5mm Hg BP subjects will receive minocycline 200 mg.
| Study group | Role | What they receive |
|---|---|---|
| Minocycline (50 mg/d) | Experimental | Subjects received minocycline 50mg/d. Receives: Drug: Minocycline 50mg/d |
| Minocycline (100 mg/d) | Experimental | Subjects received minocycline 50mg escalating to 100 mg/d. Receives: Drug: Minocycline 100mg/d |
| Minocycline (200 mg/d) | Experimental | Subjects received minocycline 50mg escalating to 100 mg then 200 mg/d. Receives: Device: Minocycline 200mg/d |
What is being measured
The primary outcome is the main question the study is designed to answer.
Categorical Classification of Subjects Into Responders vs. Non-responders
The primary measure of interest was the categorical classification of subjects into responders vs. non-responders upon treatment with a specific minocycline dose: 50, 100 or 200 mg/d. Responders are defined as subjects who achieve a drop of >5 mmHg in mean daytime SBP, based on daytime ABPM measurements (7 am to 10 pm). For these participants, the discontinuation or lowering of the dose of a concurrent anti-hypertensive drug due to excessive SBP reduction will also be assessed. Excessive SBP reduction is defined as an office SBP <120 mmHg or >10 mmHg SBP decrease associated with symptom(s). On the other hand, non-responders are defined as the participants that fail to show any change in their average daytime SBP measured through ABPM despite being exposed to the different minocycline doses evaluated.
Measured: 180 days
Secondary outcomes (2)
Change in 24 Hour SBP by ABPM
Among Responders, difference in overall daytime and nighttime Systolic Blood Pressure (SBP) using 24 hour Ambulatory Blood Pressure Monitoring (ABPM) from baseline to final visit
Measured: 180 days
Changes in Office SBP Over Time
Among Responders, evaluation of changes in office systolic blood pressure (SBP) from baseline to final visit
Measured: 180 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 May 2014 (estimated)
- Study startOct 2014
- Primary completion1 Nov 2018
- Study completion1 Nov 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HypertensionStudies of the same condition, open and under way.
- More trials run by University of FloridaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- Open label, dose effectiveness trial
- Masking
- None (open label)
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Sponsor
- Investigators
- Carl Pepine, MD, Principal investigator, University of Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02133872
- Sponsor's protocol ID
- IRB2015005 -N
- Other IDs
- RO1HL3361028, 2013-00102 Study 1, 1R01HL132448-01
- Status last verified
- Oct 2025
- First submitted
- 6 May 2014
- Last updated
- 23 Oct 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Angiotensin and Neuroimmune Activation in Hypertension
- ClinicalTrials.gov ID
- NCT02133872
- Acronym / sponsor ID
- IRB2015005 -N
- Conditions
- Hypertension
- Keywords
- Resistent Hypertension
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- University of FloridaUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Oct 2014
- Primary completion
- 1 Nov 2018 (actual)
- Study completion
- 1 Nov 2018 (actual)
- First posted
- 8 May 2014 (estimated)
- Results
- Posted 23 Oct 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Open-label design of dose titration for each participant beginning at 50 mg/day of minocycline, escalating to 100 mg/day and 200 mg/day if the primary outcome measure of ambulatory blood pressure monitor (ABPM) =/> to 5 mmHg decrease in mean daytime SBP was not achieved. If patients responded, participation was completed. This revised protocol was resubmitted to the IRB and approved on 1/6/16. An interim analysis was planned after 40 patients completed the revised protocol.
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 be fitted with an ABPM system. Patients will wear the ABPM for 24 hours at which point they will mail the monitor back to research personnel. 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, selected cytokines, markers of gut permeability including zonulin, 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 and nighttime. 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.).
If patients respond to treatment, by protocol defined drop in daytime ABPM and/or the need for down titration of hypertensive therapy they will be considered a responder, complete the final visit and complete study participation. At the final visit, the same blood tests at baseline will be repeated. When the patients complete the 6 months of treatment or are considered a responder at a lower dose, they will come in for their final visit, and return the ABPM monitor, their participation in the trial will be considered as complete.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Open label, dose effectiveness trial
| Arm | Type | Receives |
|---|---|---|
| Minocycline (50 mg/d) | Experimental | Drug: Minocycline 50mg/dSubjects received minocycline 50mg/d. |
| Minocycline (100 mg/d) | Experimental | Drug: Minocycline 100mg/dSubjects received minocycline 50mg escalating to 100 mg/d. |
| Minocycline (200 mg/d) | Experimental | Device: Minocycline 200mg/dSubjects received minocycline 50mg escalating to 100 mg then 200 mg/d. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Greater than 18 and less than 86 years of age;
- On stable medication regimen
- Full-tolerated doses of 3 or more antihypertensive medications of different classes, one of which must be a diuretic (with no changes for a minimum of two months prior to screening) that is expected to be maintained without changes for at least 3 months.
- The individual agrees to have all study procedures performed
- Willing to provide written consent
Key exclusion criteria (7 listed)
- eGFR of < 45mL/min/1.73m2, using the MDRD calculation.
- More than one in-patient hospitalization for an antihypertensive crisis within the year.
- More than one episode(s) of orthostatic hypotension (reduction of SBP of ≥ 20mmHg of diastolic blood pressure (DBP) of ≥ 10mmHg within 3 minutes of standing).
- Known hypersensitivity or contraindication to Minocycline or other tetracycline.
- Evidence of alcoholism or drug abuse;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Minocycline 50mg/dSubjects will receive minocycline 50mg if no mean daytime ABPM SBP decline =/> 5mm Hg; subjects will receive minocycline 100mg, if no mean daytime ABPM SBP decline =/> 5mm Hg BP subjects will receive minocycline 200 mg. | Drug | Minocycline (50 mg/d) |
| Minocycline 100mg/dSubjects will receive minocycline 50mg if no mean daytime ABPM SBP decline =/> 5mm Hg; subjects will receive minocycline 100mg, if no mean daytime ABPM SBP decline =/> 5mm Hg BP subjects will receive minocycline 200 mg. | Drug | Minocycline (100 mg/d) |
| Minocycline 200mg/dSubjects will receive minocycline 50mg if no mean daytime ABPM SBP decline =/> 5mm Hg; subjects will receive minocycline 100mg, if no mean daytime ABPM SBP decline =/> 5mm Hg BP subjects will receive minocycline 200 mg. | Device | Minocycline (200 mg/d) |
Primary outcome
Categorical Classification of Subjects Into Responders vs. Non-responders
Time frame: 180 days
The primary measure of interest was the categorical classification of subjects into responders vs. non-responders upon treatment with a specific minocycline dose: 50, 100 or 200 mg/d. Responders are defined as subjects who achieve a drop of >5 mmHg in mean daytime SBP, based on daytime ABPM measurements (7 am to 10 pm). For these participants, the discontinuation or lowering of the dose of a concurrent anti-hypertensive drug due to excessive SBP reduction will also be assessed. Excessive SBP reduction is defined as an office SBP <120 mmHg or >10 mmHg SBP decrease associated with symptom(s). On the other hand, non-responders are defined as the participants that fail to show any change in their average daytime SBP measured through ABPM despite being exposed to the different minocycline doses evaluated.
2 secondary outcomes
Change in 24 Hour SBP by ABPM
Time frame: 180 days
Changes in Office SBP Over Time
Time frame: 180 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Oct 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Carl Pepine, MD principal investigator
University of Florida
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Minocycline 50mg/d, Minocycline 100mg/d and Minocycline 200mg/d in people with Hypertension, run by University of Florida at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Oct 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Categorical Classification of Subjects Into Responders vs. Non-responders (time frame: 180 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Oct 2025.