Opioid-Related DisordersPhase 1NCT00295308
Clonidine for Relapse Prevention in Buprenorphine-Maintenance Patients
A Phase 1 study testing Clonidine in people with Opioid-Related Disorders, run by National Institute on Drug Abuse (NIDA) at 1 site in United States.
Trial summary
Background: Though the drug buprenorphine effectively treats dependence on opioids like heroin, some abstinent patients relapse to use during treatment. This relapse may be triggered by stress or stressful situations, and buprenorphine probably has no specific protective effect in these situations. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Opioid-Related Disorders
- What is being tested?
- Clonidine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 208 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Nov 2005to 30 Jul 2014
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Age between 18 and 60
- Evidence of physical dependence on opioids (self-report, urine screen, physical exam)
- Seeking treatment for opioid dependence
- Able to attend treatment clinic 7 days/week
Who cannot join
- General-
- Poor venous access
- Urologic conditions that would inhibit urine collection
- Pregnancy or breastfeeding
- Failure to agree to use a medically effective form of contraception while in the study (in women who are sexually active with a male partner and able to get pregnant). Acceptable forms of contraception for this study include: hormonal contraceptives (birth control pills, injectable hormones, vaginal ring hormones), surgical sterility (tubal ligation or hysterectomy); IUD; Diaphragm with spermicide; Condom with spermicide
- Current physical dependence on alcohol or sedative-hypnotics, e.g. benzodiazepines
Show all 56Show fewer
- Psychiatric-
- Cognitive impairment severe enough to preclude informed consent or valid responses on questionnaires (Shipley Institute of Living scale estimated full-scale IQ less than 80)
- History of schizophrenia or any other DSM-IV psychotic disorder
- History of bipolar disorder
- Current Major Depressive Disorder
- Medical-
- Any active or untreated medical illness that in the view of the investigators would compromise participation in research
- Allergy or intolerance to either buprenorphine or clonidine
- Cerebrovascular disease
- Conduction disturbances (e.g., second-degree heart block, third-degree heart block, atrial fibrillation, ventricular tachycardia) or arrhythmias
- Myocardial infarction, or documented coronary artery disease
- Congestive heart failure
- Chronic renal failure, as estimated by Cr > 2.0
- CD4 < 200 or evidence of severely compromised immune system /AIDS
- Marked, sustained bradycardia (HR < 45 bpm) on three separate occasions
- Marked, sustained low blood pressure (SBP <95 or DBP < 40 mm Hg) over three separate readings
- Marked, sustained high blood pressure (SBP >160 mm Hg, DBP >100 mm Hg) over several readings, without being on antihypertensive medications.
- ECG changes suggestive of acute ischemia, clinical important arrhythmia, left bundle branch block, or other changes that concerns the MRP will exclude the participant. If accompanied by cardiovascular complaints such as chest pain or syncope, less specific ECG findings will also exclude the patient. When in doubt, the ECG will be sent to cardiology on a prn basis for a manual reading.
- Orthostatic hypotension (upon standing for 3 minutes, there is a 20 mm Hg decrease in systolic blood pressure or a 10 mmHg decrease in diastolic blood pressure accompanied by an increase by 20 bpm in heart rate) on two separate readings.
- Taking contraindicated medications-
- Beta blockers
- Tricyclic antidepressants
- Antipsychotics
- Mah huang
- Yohimbe
- Ephedra
- Sildenafil citrate (Viagra). Sildenafil citrate doses > 25mg should not be taken within 4 hours of taking an alpha blocker or it can produce significant and symptomatic hypotension (Pfizer). Of note, Viagra, like buprenorphine, is metabolized by cytochrome P450 3A4. Ingestion of buprenorphine could potentate the effects of sildenafil citrate which could extent the period of safety to > 4 hrs from when an alpha blocker could be taken after Viagra ingestion.
- Family history of sudden cardiac death at age < 50
- Lab Test and Lab Values:
- WBC < 1,500 > 13,000 #/CUMM
- HCT < 33 > 49 Percent
- Platelets < 100 > 500 K/CUMM
- Sodium < 132 > 149 MEQ/L
- Potassium < 3.5 > 5.2 MEQ/L
- Calcium < 8.4 > 10.5 MG/DL
- Magnesium < 1.3 > 3 MG/DL
- <TAB>
- BUN > 35 MG/DL
- Cr<TAB> > 2.0 MG/DL
- <TAB>
- Alk Phos<TAB> > 200 U/L
- AST<TAB> > 200 U/L
- ALT<TAB> > 200 U/L
- GGT<TAB> > 400 U/L
- Albumin<TAB> < 3 GM/DL
- Total bilirubin > 2.0 MG/DL
- Direct bilirubin > 0.4 MG/DL
- TSH<TAB> < 0.27 > 4.2 UIU/ML
- <TAB>
- Leukocytosis will prompt further investigation before clearance.<TAB>
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institute on Drug Abuse
Baltimore, Maryland, 21224
About this study
Background:
- Though the drug buprenorphine effectively treats dependence on opioids like heroin, some abstinent patients relapse to use during treatment. This relapse may be triggered by stress or stressful situations, and buprenorphine probably has no specific protective effect in these situations. Buprenorphine probably also has no specific effect on relapse to cocaine use.
- Research has shown that clonidine, a drug originally prescribed to treat high blood pressure and some symptoms of opioid withdrawal, can help block stress-induced relapse to heroin and cocaine seeking in rats. Researchers are interested in studying whether a combination of clonidine and buprenorphine may be more effective in preventing drug relapse than administering one of the medications alone.
Read more
Objectives:
- To determine whether clonidine, given to abstinent patients maintained on buprenorphine, is more effective than placebo in preventing relapse to heroin or cocaine use.
Eligibility:
- Individuals between 18 and 50 years of age who are current cocaine or heroin users seeking treatment.
Design:
- The study will last up to 36 weeks, with four phases of treatment and a follow-up evaluation. Three times a week, participants will be asked to report illicit drug use and provide urine and breath samples. Throughout the study, participants will receive individual counseling in weekly 40 60 minute sessions. Other samples and tests will be scheduled as required by the study researchers.
- Patients will be stabilized on daily buprenorphine over the first 14 days of the study.
- Weeks 1 8: Participants will receive vouchers for regular substance-free urine samples. Those who successfully complete this phase will continue to the next part of the study.
- Weeks 7 9: Participants will receive either clonidine or placebo along with the buprenorphine. The dose of clonidine will be stabilized during this time.
- Weeks 9 22: Participants will continue to receive either clonidine or placebo along with the buprenorphine. During this part of the study, participants will keep electronic diaries to record drug use or craving and to record data on mood, stress levels, and activity.
- Weeks 23 28: Participants will stop taking the clonidine or placebo, but will continue the buprenorphine treatment. Participants will continue to keep electronic diaries.
- Weeks 29 36: Participants will have the choice of transferring to a community clinic transfer or gradually reducing doses of buprenorphine to end the study.
- Participants will return for a follow-up visit and urine sample 6 months after the end of the study.
Read the detailed description
Background. Though buprenorphine effectively treats opioid dependence, some abstinent patients relapse to maladaptive use of opioids during treatment. Relapse may be triggered by stress. Rodent studies have demonstrated that stress can induce relapse to heroin and cocaine use (Erb, et al., 1996; Shaham, et al., 1996; Shaham and Stewart, 1995). In a rodent model, stress-induced relapse to heroin and cocaine seeking is blocked by the alpha-2 adrenergic agonist clonidine. In this study, clonidine will be compared to placebo in preventing relapse to opioid abuse in opioid maintained patients who have achieved abstinence while on buprenorphine and contingency management.
Scientific goals. To determine whether clonidine, given to abstinent patients maintained on buprenorphine, prevents relapse to opioid use more effectively than placebo.
Participant population. 300 opioid-dependent outpatients (120 evaluable). Target enrollment will include 40 persent women and 60 percent minorities (mostly African-American).
Experimental design and methods. The study will be a randomized double-blind clinical trial. Two treatment groups will be studied (60/group), one receiving clonidine and the other receiving placebo. Assignment to treatment group will be randomized. All patients will receive buprenorphine daily (8 mg to 24 mg SL) and individual counseling weekly throughout 28 weeks of treatment. In order to establish abstinence prior to clonidine induction, after one week of stabilization on buprenorphine, they will receive contingent vouchers for opioid-negative urine specimens for 8 weeks (weeks 1-8). Patients who are abstinent from illicit opioids during weeks 5 and 6 will be randomized to receive clonidine (0.3 mg oral dose) or clonidine placebo from weeks 9 through 20. Participants who are not abstinent will be switched to methadone for four weeks (usual dose from 50 mg to 100 mg) followed by an eight week methadone taper. Assignment to clonidine or placebo will be double-blind. Weeks 21 and 22 will include a clonidine taper to avoid rebound hypertension. From weeks 23-28, participants will receive buprenorphine and counseling only, and then will be offered assistance to transfer to another program; those who do not transfer will undergo an 8-week buprenorphine taper. The primary outcome measures will be longest duration of opioid abstinence, time to relapse, and the proportion of opioid-negative urine specimens over time during the Intervention phase. In addition, fluctuations in drug use, drug craving, stress, and HIV-risk behaviors such as injection drug use will be assessed via ecological momentary assessment (EMA).
Benefits to participants and/or society. Participants will receive buprenorphine, drug counseling, and contingency-management therapy. The buprenorphine and voucher interventions are likely to reduce participants' use of opioids. Counseling will include reduction of HIV risk behaviors.
Risks to participants. Participants may experience side effects from clonidine, buprenorphine, or methadone and discomfort during withdrawal from each drug. In particular, discontinuation of clonidine may cause rebound hypertension. The EMA component of the study may generate some assessment burden.
- Conditions
- Opioid-Related Disorders
- Being tested
- Clonidine, Placebo
- Keywords
- Opioid Dependence, Clonidine, Buprenorphine, Opioid Abstinence, Relapse
- Medical subject headings
- Opioid-Related Disorders, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ClonidineDrug
clonidine up to 0.3 mg/day oral
PlaceboDrug
oral capsules daily
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | Not described Receives: Drug: Clonidine |
| Arm 2 | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Opiate-negative urine screens
Measured: 38 weeks
Secondary outcomes (2)
HIV risk behaviors
Measured: 38 weeks
Craving
Measured: 18 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Feb 2006 (estimated)
- Study start8 Nov 2005
- Study completion30 Jul 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Opioid-Related DisordersStudies of the same condition, open and under way.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Enrolment
- 208 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute on Drug Abuse (NIDA)
- Sponsor type
- US National Institutes of Health
- Investigators
- Kenzie Preston, Ph.D., Principal investigator, National Institute on Drug Abuse (NIDA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00295308
- Sponsor's protocol ID
- 999906407
- Other IDs
- 06-DA-N407
- Status last verified
- 17 Sep 2014
- First submitted
- 22 Feb 2006
- Last updated
- 17 Dec 2019
- Results posted
- No
Publications
Kowalczyk WJ, Moran LM, Bertz JW, Phillips KA, Ghitza UE, Vahabzadeh M, Lin JL, Epstein DH, Preston KL. Using ecological momentary assessment to examine the relationship between craving and affect with opioid use in a clinical trial of clonidine as an adjunct medication to buprenorphine treatment. Am J Drug Alcohol Abuse. 2018;44(5):502-511. doi: 10.1080/00952990.2018.1454933. Epub 2018 Apr 10.
PubMed 29634425Kowalczyk WJ, Phillips KA, Jobes ML, Kennedy AP, Ghitza UE, Agage DA, Schmittner JP, Epstein DH, Preston KL. Clonidine Maintenance Prolongs Opioid Abstinence and Decouples Stress From Craving in Daily Life: A Randomized Controlled Trial With Ecological Momentary Assessment. Am J Psychiatry. 2015 Aug 1;172(8):760-7. doi: 10.1176/appi.ajp.2014.14081014. Epub 2015 Mar 17.
PubMed 25783757
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clonidine for Relapse Prevention in Buprenorphine-Maintenance Patients
- ClinicalTrials.gov ID
- NCT00295308
- Acronym / sponsor ID
- 999906407
- Conditions
- Opioid-Related Disorders
- Keywords
- Opioid Dependence, Clonidine, Buprenorphine, Opioid Abstinence, Relapse
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 208 participants (actual)
- Lead sponsor
- National Institute on Drug Abuse (NIDA)US National Institutes of Health
- Study start
- 8 Nov 2005
- Study completion
- 30 Jul 2014 (actual)
- First posted
- 23 Feb 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
- Though the drug buprenorphine effectively treats dependence on opioids like heroin, some abstinent patients relapse to use during treatment. This relapse may be triggered by stress or stressful situations, and buprenorphine probably has no specific protective effect in these situations. Buprenorphine probably also has no specific effect on relapse to cocaine use.
- Research has shown that clonidine, a drug originally prescribed to treat high blood pressure and some symptoms of opioid withdrawal, can help block stress-induced relapse to heroin and cocaine seeking in rats. Researchers are interested in studying whether a combination of clonidine and buprenorphine may be more effective in preventing drug relapse than administering one of the medications alone.
Objectives:
- To determine whether clonidine, given to abstinent patients maintained on buprenorphine, is more effective than placebo in preventing relapse to heroin or cocaine use.
Eligibility:
- Individuals between 18 and 50 years of age who are current cocaine or heroin users seeking treatment.
Design:
- The study will last up to 36 weeks, with four phases of treatment and a follow-up evaluation. Three times a week, participants will be asked to report illicit drug use and provide urine and breath samples. Throughout the study, participants will receive individual counseling in weekly 40 60 minute sessions. Other samples and tests will be scheduled as required by the study researchers.
- Patients will be stabilized on daily buprenorphine over the first 14 days of the study.
- Weeks 1 8: Participants will receive vouchers for regular substance-free urine samples. Those who successfully complete this phase will continue to the next part of the study.
- Weeks 7 9: Participants will receive either clonidine or placebo along with the buprenorphine. The dose of clonidine will be stabilized during this time.
- Weeks 9 22: Participants will continue to receive either clonidine or placebo along with the buprenorphine. During this part of the study, participants will keep electronic diaries to record drug use or craving and to record data on mood, stress levels, and activity.
- Weeks 23 28: Participants will stop taking the clonidine or placebo, but will continue the buprenorphine treatment. Participants will continue to keep electronic diaries.
- Weeks 29 36: Participants will have the choice of transferring to a community clinic transfer or gradually reducing doses of buprenorphine to end the study.
- Participants will return for a follow-up visit and urine sample 6 months after the end of the study.
Detailed description
Background. Though buprenorphine effectively treats opioid dependence, some abstinent patients relapse to maladaptive use of opioids during treatment. Relapse may be triggered by stress. Rodent studies have demonstrated that stress can induce relapse to heroin and cocaine use (Erb, et al., 1996; Shaham, et al., 1996; Shaham and Stewart, 1995). In a rodent model, stress-induced relapse to heroin and cocaine seeking is blocked by the alpha-2 adrenergic agonist clonidine. In this study, clonidine will be compared to placebo in preventing relapse to opioid abuse in opioid maintained patients who have achieved abstinence while on buprenorphine and contingency management.
Scientific goals. To determine whether clonidine, given to abstinent patients maintained on buprenorphine, prevents relapse to opioid use more effectively than placebo.
Participant population. 300 opioid-dependent outpatients (120 evaluable). Target enrollment will include 40 persent women and 60 percent minorities (mostly African-American).
Experimental design and methods. The study will be a randomized double-blind clinical trial. Two treatment groups will be studied (60/group), one receiving clonidine and the other receiving placebo. Assignment to treatment group will be randomized. All patients will receive buprenorphine daily (8 mg to 24 mg SL) and individual counseling weekly throughout 28 weeks of treatment. In order to establish abstinence prior to clonidine induction, after one week of stabilization on buprenorphine, they will receive contingent vouchers for opioid-negative urine specimens for 8 weeks (weeks 1-8). Patients who are abstinent from illicit opioids during weeks 5 and 6 will be randomized to receive clonidine (0.3 mg oral dose) or clonidine placebo from weeks 9 through 20. Participants who are not abstinent will be switched to methadone for four weeks (usual dose from 50 mg to 100 mg) followed by an eight week methadone taper. Assignment to clonidine or placebo will be double-blind. Weeks 21 and 22 will include a clonidine taper to avoid rebound hypertension. From weeks 23-28, participants will receive buprenorphine and counseling only, and then will be offered assistance to transfer to another program; those who do not transfer will undergo an 8-week buprenorphine taper. The primary outcome measures will be longest duration of opioid abstinence, time to relapse, and the proportion of opioid-negative urine specimens over time during the Intervention phase. In addition, fluctuations in drug use, drug craving, stress, and HIV-risk behaviors such as injection drug use will be assessed via ecological momentary assessment (EMA).
Benefits to participants and/or society. Participants will receive buprenorphine, drug counseling, and contingency-management therapy. The buprenorphine and voucher interventions are likely to reduce participants' use of opioids. Counseling will include reduction of HIV risk behaviors.
Risks to participants. Participants may experience side effects from clonidine, buprenorphine, or methadone and discomfort during withdrawal from each drug. In particular, discontinuation of clonidine may cause rebound hypertension. The EMA component of the study may generate some assessment burden.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Experimental | Drug: Clonidine |
| Arm 2 | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
Key exclusion criteria (56 listed)
- General-
- Poor venous access
- Urologic conditions that would inhibit urine collection
- Pregnancy or breastfeeding
- Failure to agree to use a medically effective form of contraception while in the study (in women who are sexually active with a male partner and able to get pregnant). Acceptable forms of contraception for this study include: hormonal contraceptives (birth control pills, injectable hormones, vaginal ring hormones), surgical sterility (tubal ligation or hysterectomy); IUD; Diaphragm with spermicide; Condom with spermicide
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 |
|---|---|---|
| Clonidineclonidine up to 0.3 mg/day oral | Drug | Arm 1 |
| Placebooral capsules daily | Drug | Arm 2 |
Primary outcome
Opiate-negative urine screens
Time frame: 38 weeks
2 secondary outcomes
HIV risk behaviors
Time frame: 38 weeks
Craving
Time frame: 18 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2019.
- Derived from this study: PubMed 29634425Kowalczyk WJ, Moran LM, Bertz JW, Phillips KA, Ghitza UE, Vahabzadeh M, Lin JL, Epstein DH, Preston KL. Using ecological momentary assessment to examine the relationship between craving and affect with opioid use in a clinical trial of clonidine as an adjunct medication to buprenorphine treatment. Am J Drug Alcohol Abuse. 2018;44(5):502-511. doi: 10.1080/00952990.2018.1454933. Epub 2018 Apr 10.
- Derived from this study: PubMed 25783757Kowalczyk WJ, Phillips KA, Jobes ML, Kennedy AP, Ghitza UE, Agage DA, Schmittner JP, Epstein DH, Preston KL. Clonidine Maintenance Prolongs Opioid Abstinence and Decouples Stress From Craving in Daily Life: A Randomized Controlled Trial With Ecological Momentary Assessment. Am J Psychiatry. 2015 Aug 1;172(8):760-7. doi: 10.1176/appi.ajp.2014.14081014. Epub 2015 Mar 17.
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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.
Kenzie Preston, Ph.D. principal investigator
National Institute on Drug Abuse (NIDA)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Clonidine in people with Opioid-Related Disorders, run by National Institute on Drug Abuse (NIDA) 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 4 inclusion and 56 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 17 Dec 2019. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Opiate-negative urine screens (time frame: 38 weeks). 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 NCT00295308, 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 17 Dec 2019.