Low-Dose Clonidine for PTSD

Recruiting at 1 trial location

Overseen By Kevin Petranu

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Wake Forest University Health Sciences

Must be taking: Clonidine

Must not be taking: Opiates, Antipsychotics, Benzodiazepines, others

Disqualifiers: Pregnancy, Unstable mental illness, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

32 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if clonidine, a medication typically used for high blood pressure, can improve PTSD symptoms in veterans. The study will compare clonidine's effects to a placebo (a pill with no active medicine) over several weeks. Veterans with PTSD who frequently experience symptoms like nightmares or unwanted memories might be suitable candidates. Participants will have the opportunity to try both clonidine and the placebo during the study. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, including clonidine, other α2 agonists, α1-adrenergic antagonists, opiates, antipsychotics, benzodiazepines, and cyproheptadine. If you are on any of these, you may need to stop them before participating.

Is there any evidence suggesting that clonidine is likely to be safe for humans?

Research has shown that clonidine is generally a safe treatment, though it can have some common side effects. It has been used for conditions like high blood pressure, severe cancer pain, and withdrawal symptoms. Studies suggest clonidine might also help with PTSD and anxiety, even though it's not officially approved for these mental health issues.

While clonidine is considered relatively safe, some people may experience side effects such as low blood pressure, dizziness, dry mouth, and drowsiness. Discussing these possible issues with a healthcare provider is important.

Clonidine has FDA approval for other uses, which supports its safety. However, weighing the benefits against any possible risks is always important when considering this treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for PTSD?

Unlike the standard treatments for PTSD, which often include SSRIs like sertraline and paroxetine, clonidine offers a different approach. Researchers are excited about clonidine because it acts on the alpha-2 adrenergic receptors, which may help reduce hyperarousal symptoms that are common in PTSD. This mechanism is distinct from traditional antidepressants and could provide relief for those who do not respond well to existing medications. Additionally, clonidine’s potential for a quicker onset of action could mean faster symptom relief for patients.

What evidence suggests that clonidine might be an effective treatment for PTSD?

Research has shown that clonidine, a medication affecting the nervous system, may help treat PTSD symptoms. It improves sleep and reduces nightmares, common issues for those with PTSD. Studies suggest clonidine might also reduce the retention of fear memories, a major aspect of PTSD. An open-label trial in children with PTSD found clonidine very effective in reducing symptoms, offering hope for its use in adults. In this trial, participants will receive clonidine in one phase and a placebo in another, as part of a crossover design. Overall, clonidine appears to be a promising treatment option to ease PTSD symptoms, though further research is beneficial. ^{6 7 8 9 10}

Who Is on the Research Team?

Michael Fendrich, PhD

Principal Investigator

Wake Forest University Health Sciences

Gregory Burek, MD, MS

Principal Investigator

Wake Forest University Health Sciences

Are You a Good Fit for This Trial?

This trial is for US military veterans over 18 with PTSD, who have specific scores on the PCL5 and CAPS assessments indicating intrusion or nightmares. Participants must speak English and be willing to visit the clinic as required. Excluded are those with certain heart conditions, severe hypertension, kidney disease, recent heart attack or stroke, drug use disorders, other mental health issues that could interfere with participation, or those taking conflicting medications.

Inclusion Criteria

You are a former member of the US military.

You have experienced traumatic events and have symptoms such as flashbacks or nightmares (PCL5 items 1-5) or avoidance of thoughts or feelings related to the event (PCL5 items 15-20) with a score of 10 or higher.

Willing to come into the clinic as programmed

Exclusion Criteria

I am taking Catapres or Kapvay (clonidine).

I am taking Aldomet (Methyldopa).

You have used or are currently using cannabis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Clonidine Phase

Participants receive clonidine titrations across 6 weeks

6 weeks

Weekly visits (in-person or virtual)

Placebo Phase

Participants receive placebo titrations across 6 weeks

6 weeks

Weekly visits (in-person or virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Clonidine
• Placebo

Trial Overview The study tests if low-dose clonidine can improve PTSD symptoms in veterans compared to a placebo. The hypothesis suggests benefits in daytime behavior and sleep-related issues. Participants will receive either clonidine pills or a placebo without knowing which one they're getting.

How Is the Trial Designed?

Group I: Clonidine Phase Experimental Treatment 1 Intervention

Participants will receive clonidine titrations across 6 weeks. Note that this is a crossover design, so patients will move across phases.

Group II: Placebo Phase Placebo Group 1 Intervention

Participants will receive placebo titrations across 6 weeks. Note that this is a crossover design, so patients will move across phases.

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?

Wake Forest University Health Sciences

Lead Sponsor

Trials

1,432

Recruited

2,506,000+

Aurora Health Care

Lead Sponsor

Trials

46

Recruited

16,400+

Published Research Related to This Trial

Clonidine is a safe and effective medication for detoxifying certain opiate addicts, particularly as a transitional treatment before starting naltrexone for aftercare.

The rising cocaine abuse epidemic in the U.S. may necessitate hospitalization or specialized outpatient programs for effective treatment, highlighting the need for structured care in managing addiction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Opiate and cocaine dependencies. Techniques to help counter the rising tide. Washton, AM., Gold, MS., Pottash, AC.[2019]

A new method for measuring clonidine levels in human plasma was developed, involving a simple extraction and derivatization process, which allows for accurate detection at very low concentrations (1 ng/ml) with a precision of +/- 2.4%.

This method utilizes advanced gas chromatography and mass spectrometry techniques, making it effective for monitoring clonidine, an important antihypertensive medication, in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Determination of clonidine in human plasma by cold on-column injection capillary gas chromatography-selected-ion monitoring-mass spectrometry. Arrendale, RF., Stewart, JT., Tackett, RL.[2013]

Clonidine and prazosin are both effective in treating nighttime symptoms of posttraumatic stress disorder (PTSD), providing relief for patients suffering from these specific symptoms.

However, the long-term use of these medications may be restricted, suggesting a need for careful management and consideration of alternative treatments for sustained care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Clonidine and Prazosin for the Treatment of Nighttime Posttraumatic Stress Disorder Symptoms. Wendell, KR., Maxwell, ML.[2023]

In a study of 79 veterans with moderate to severe PTSD, treatment with low-dose clonidine resulted in 72% of patients showing improvement in their symptoms, with 49% reporting significant improvement.

The study indicated that clonidine is generally safe, with only 18 out of 79 patients experiencing adverse effects, suggesting it could be a viable treatment option for managing PTSD symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-dose clonidine in veterans with Posttraumatic stress disorder. Burek, GA., Waite, MR., Heslin, K., et al.[2021]

A case report of a U.S. veteran with PTSD showed that clonidine effectively controlled her nightmare symptoms, which returned when the medication was stopped and resolved again upon resuming treatment.

Clonidine may work by altering REM and non-REM sleep patterns or influencing memory consolidation, suggesting its potential as a therapeutic option for nightmares in PTSD, although further formal trials are needed to confirm its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clonidine Use for the Treatment of Nightmares in Posttraumatic Stress Disorder. Bange, JS., Melvin, KE.[2022]

Transdermal clonidine (M-5041T) demonstrated a gradual increase and decrease in plasma clonidine levels, leading to a longer elimination half-life compared to oral clonidine (Catapres), suggesting a more stable delivery method.

The blood pressure-lowering effects of both M-5041T and Catapres were similar, but M-5041T was associated with fewer adverse symptoms, indicating it may be a safer option for treating hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the pharmacokinetics, pharmacodynamics, and safety of oral (Catapres) and transdermal (M-5041T) clonidine in healthy subjects. Fujimura, A., Ebihara, A., Ohashi, K., et al.[2019]

Clonidine, an alpha 2-adrenergic receptor agonist, interacts with multiple neurotransmitter systems and has shown potential benefits in treating various neuropsychiatric conditions, including Tourette's syndrome and migraine.

Despite its efficacy in these conditions, the abstract emphasizes the importance of long-term evaluations to fully understand clonidine's safety and effectiveness in these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clonidine in neuropsychiatric disorders: a review. Sandyk, R., Gillman, MA., Iacono, RP., et al.[2019]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38941125/

Clonidine for post-traumatic stress disorder: a systematic ... Clonidine, a central adrenergic antagonist, shows promise in improving sleep, nightmares, and PTSD symptoms, but further research is needed.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT07044609

NCT07044609 | A Study to Assess the Effectiveness and ... The primary objective of this study is to establish that an optimal dose of OnydaTM XR will result in a significant reduction in attention- ...

3. nature.com nature.com/articles/npp2012145

Preclinical Evaluation of Reconsolidation Blockade by ... All tested doses of clonidine showed effectiveness in reducing postreactivation fear memory retention in a long-lasting and dose-dependent ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12559684/

Repurposing Existing Drugs for the Treatment of Post ... Clonidine, an alpha-2 adrenergic agonist, showed promise in improving PTSD symptoms, particularly sleep disturbances and nightmares. It was ...

5. cureus.com cureus.com/articles/211807-alpha-2-agonists-in-children-and-adolescents-with-post-traumatic-stress-disorder-a-systematic-review

Alpha-2 Agonists in Children and Adolescents With Post ... In an open-label trial [36], clonidine was tried on seven preschool children and was found to be highly effective in reducing PTSD symptoms. ...

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

Clonidine - StatPearls - NCBI Bookshelf ... post-traumatic stress disorder (PTSD). While the drug is relatively safe, it is essential to discuss any potential contraindications and adverse effects ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3926778/

Safety and efficacy of clonidine and clonidine extended ... Clonidine and clonidine extended-release have been shown to have efficacy in the treatment of ADHD. However, the studies contain significant flaws.

8. go.drugbank.com go.drugbank.com/drugs/DB00575

Clonidine: Uses, Interactions, Mechanism of Action Clonidine is an alpha-2 adrenergic agonist used to treat hypertension and severe cancer pain, among other conditions, and to treat withdrawal symptoms from ...

9. medvidi.com medvidi.com/blog/catapres-clonidine-for-anxiety-uses-facts-and-side-effects

Clonidine (Catapres) for Anxiety: Uses, Benefits, and Dosage Clonidine is sometimes prescribed off-label to help with generalized anxiety disorder (GAD), post-traumatic stress disorder (PTSD), and other ...

10. uptodate.com uptodate.com/contents/posttraumatic-stress-disorder-in-children-and-adolescents-treatment-overview

Posttraumatic stress disorder in children and adolescents Clonidine – We typically start at 0.05 to 0.1 mg at night, increase by 0.05 to 0.1 mg every three nights to a maximum dose of 0.2 to 0.5 mg/day.