Type 2 DiabetesPhase 4DOXYNCT01375491
Examination of the Anti-inflammatory and Insulin Sensitizing Properties of Doxycycline in Humans
A Phase 4 study testing Doxycycline in people with Type 2 Diabetes and Obesity, run by University of California, San Diego at 1 site in United States.
Trial summary
Obesity is a heightened state of inflammation in which production of cytokines and matrix metalloproteinases (MMPs) result in loss of function of insulin receptors and insulin resistance. Doxycycline (DOX) is a potent MMP inhibitor. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Type 2 Diabetes, Obesity
- What is being tested?
- Doxycycline
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 39 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2009to Jun 2011
- Phase
- Phase 4
- 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 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Ambulatory, medically stable, able to give informed consent, and comply with the protocol.
- Obesity with BMI >30 kg/m2.
- DM2 for less than 10 years.
- 7.5% < HA1C < 10%
- Taking insulin and/or oral medications (biguanide, sulfonlylurea, etc.)
Who cannot join
- Mental states that would preclude complete understanding of the protocol and compliance.
- Chronic illness such as renal failure (with creatinine clearance <80 ml/min for Specific Aim 2).
- Women of child-bearing age because of the potential hazard to the fetus (doxycycline may cause permanent discoloration of the teeth and deposition in bone inhibiting growth) and because doxycycline may render oral contraceptives less effective.
- Nursing mothers.
- Allergy to tetracyclines.
- Subjects taking the following drugs: penicillin or it's derivatives, anticoagulant therapy, antacids containing aluminum, calcium, or magnesium, iron-containing preparations, bismuth subsalicylate, barbiturates, carbamazepine, phenytoin or methoxyflurane, thiazolidinediones (TZD)
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California San Diego Clinical trials Research Institute
La Jolla, California, 92093
About this study
Official title: Blockade of Receptor Cleavage in Diabetes Mellitus With an MMP Inhibitor
Obesity is a heightened state of inflammation in which production of cytokines and matrix metalloproteinases (MMPs) result in loss of function of insulin receptors and insulin resistance. Doxycycline (DOX) is a potent MMP inhibitor. We hypothesize that DOX will enhance insulin sensitivity and decreases inflammation in obese participants with type 2 diabetes (DM2).
Read the detailed description
Design and Setting: 84 day (D84), double-blind, randomized, placebo (PL)-controlled clinical trial conducted in an academic tertiary care center.
Patients: Non-DM2 Controls (n=15); participants with DM2 receiving PL (n=13) or DOX (n=11).
Interventions: All participants were evaluated at day 1 (D1); those with DM2 were also evaluated at D84 after DOX 100mg twice daily or PL.
- Conditions
- Type 2 Diabetes, Obesity
- Being tested
- Doxycycline, Placebo
- Keywords
- doxycycline, insulin resistance, obesity, inflammation
- Medical subject headings
- Diabetes Mellitus, Type 2, Obesity, Insulin Resistance, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DoxycyclineDrug
Also called Vibramycin
generic doxycycline 100mg twice daily
PlaceboOther
Placebo comparator to doxycycline
| Study group | Role | What they receive |
|---|---|---|
| Doxycycline | Experimental | Participants with DM2 receiving doxycycline 100mg BID Receives: Drug: Doxycycline |
| Placebo | Placebo comparator | Pills prepared identical to doxycycline. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
MMP Activity
MMP activity is measured using a charge-changing peptide substrate for MMP-2 and MMP-9.
Measured: Baseline (Day 1)
MMP Activity
MMP activity is measured using a charge-changing peptide substrate for MMP-2 and MMP-9. Only the Doxycycline and Placebo arms are reported because the control group was not evaluated at Day 84.
Measured: Day 84
Secondary outcomes (2)
CRP
Measure of global inflammation.
Measured: Baseline (Day 1)
CRP
Measure of global inflammation. Only the Doxycycline and Placebo arms are reported because the control group was not evaluated at Day 84.
Measured: Day 84
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jun 2011 (estimated)
- Study startOct 2009
- Primary completionJun 2011
- Study completionJun 2011
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.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Type 2 DiabetesStudies of the same condition, open and under way.
- More trials run by University of California, San DiegoThe 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 39 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Diego
- Sponsor type
- University, hospital or other
- Collaborators
- Ruth L. Kirschstein National Research Service Award, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Center for Research Resources (NCRR)
- Responsible party
- Sponsor
- Investigators
- Karen L Herbst, PhD, MD, Principal investigator, UCSD
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01375491
- Sponsor's protocol ID
- 090395
- Other IDs
- 5M01RR000827, P30DK063491
- Acronym
- DOXY
- Status last verified
- Jan 2020
- First submitted
- 25 May 2011
- Last updated
- 13 Jan 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
DeLano FA, Schmid-Schonbein GW. Proteinase activity and receptor cleavage: mechanism for insulin resistance in the spontaneously hypertensive rat. Hypertension. 2008 Aug;52(2):415-23. doi: 10.1161/HYPERTENSIONAHA.107.104356. Epub 2008 Jul 7.
PubMed 18606910Frankwich K, Tibble C, Torres-Gonzalez M, Bonner M, Lefkowitz R, Tyndall M, Schmid-Schonbein GW, Villarreal F, Heller M, Herbst K. Proof of Concept: Matrix metalloproteinase inhibitor decreases inflammation and improves muscle insulin sensitivity in people with type 2 diabetes. J Inflamm (Lond). 2012 Oct 1;9(1):35. doi: 10.1186/1476-9255-9-35.
PubMed 23025537
Study at a glance
From the registry record, last updated by the sponsor on 13 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Blockade of Receptor Cleavage in Diabetes Mellitus With an MMP Inhibitor
- ClinicalTrials.gov ID
- NCT01375491
- Acronym / sponsor ID
- DOXY / 090395
- Conditions
- Type 2 Diabetes, Obesity
- Keywords
- doxycycline, insulin resistance, obesity, inflammation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 39 participants (actual)
- Lead sponsor
- University of California, San DiegoUniversity, hospital or other
- Collaborators
- Ruth L. Kirschstein National Research Service Award, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Center for Research Resources (NCRR)
- Study start
- Oct 2009
- Primary completion
- Jun 2011 (actual)
- Study completion
- Jun 2011 (actual)
- First posted
- 17 Jun 2011 (estimated)
- Results
- Posted 13 Jan 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Obesity is a heightened state of inflammation in which production of cytokines and matrix metalloproteinases (MMPs) result in loss of function of insulin receptors and insulin resistance. Doxycycline (DOX) is a potent MMP inhibitor. We hypothesize that DOX will enhance insulin sensitivity and decreases inflammation in obese participants with type 2 diabetes (DM2).
Detailed description
Design and Setting: 84 day (D84), double-blind, randomized, placebo (PL)-controlled clinical trial conducted in an academic tertiary care center.
Patients: Non-DM2 Controls (n=15); participants with DM2 receiving PL (n=13) or DOX (n=11).
Interventions: All participants were evaluated at day 1 (D1); those with DM2 were also evaluated at D84 after DOX 100mg twice daily or PL.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Doxycycline | Experimental | Drug: DoxycyclineParticipants with DM2 receiving doxycycline 100mg BID |
| Placebo | Placebo comparator | Other: PlaceboPills prepared identical to doxycycline. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Ambulatory, medically stable, able to give informed consent, and comply with the protocol.
- Obesity with BMI >30 kg/m2.
- DM2 for less than 10 years.
- 7.5% < HA1C < 10%
- Taking insulin and/or oral medications (biguanide, sulfonlylurea, etc.)
Key exclusion criteria (6 listed)
- Mental states that would preclude complete understanding of the protocol and compliance.
- Chronic illness such as renal failure (with creatinine clearance <80 ml/min for Specific Aim 2).
- Women of child-bearing age because of the potential hazard to the fetus (doxycycline may cause permanent discoloration of the teeth and deposition in bone inhibiting growth) and because doxycycline may render oral contraceptives less effective.
- Nursing mothers.
- Allergy to tetracyclines.
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 |
|---|---|---|
| DoxycyclineAlso: Vibramycingeneric doxycycline 100mg twice daily | Drug | Doxycycline |
| PlaceboPlacebo comparator to doxycycline | Other | Placebo |
Primary outcome
MMP Activity
Time frame: Baseline (Day 1)
MMP activity is measured using a charge-changing peptide substrate for MMP-2 and MMP-9.
MMP Activity
Time frame: Day 84
MMP activity is measured using a charge-changing peptide substrate for MMP-2 and MMP-9. Only the Doxycycline and Placebo arms are reported because the control group was not evaluated at Day 84.
2 secondary outcomes
CRP
Time frame: Baseline (Day 1)
CRP
Time frame: Day 84
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jan 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 18606910DeLano FA, Schmid-Schonbein GW. Proteinase activity and receptor cleavage: mechanism for insulin resistance in the spontaneously hypertensive rat. Hypertension. 2008 Aug;52(2):415-23. doi: 10.1161/HYPERTENSIONAHA.107.104356. Epub 2008 Jul 7.
- Results publication: PubMed 23025537Frankwich K, Tibble C, Torres-Gonzalez M, Bonner M, Lefkowitz R, Tyndall M, Schmid-Schonbein GW, Villarreal F, Heller M, Herbst K. Proof of Concept: Matrix metalloproteinase inhibitor decreases inflammation and improves muscle insulin sensitivity in people with type 2 diabetes. J Inflamm (Lond). 2012 Oct 1;9(1):35. doi: 10.1186/1476-9255-9-35.
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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.
Karen L Herbst, PhD, MD principal investigator
UCSD
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Doxycycline in people with Type 2 Diabetes and Obesity, run by University of California, San Diego 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 6 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 13 Jan 2020. 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. Some participants in this study may receive a placebo. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 13 Jan 2020). 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?
MMP Activity (time frame: Baseline (Day 1)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01375491, which also lists 2 linked publications.
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 13 Jan 2020.