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

Trial Summary

What is the purpose of this trial?

Hypothesis: Veterans with PTSD prescribed clonidine will demonstrate improvements in PTSD symptoms, including daytime, nighttime, and sleep-related behaviors.

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.

What evidence supports the effectiveness of the drug clonidine for treating PTSD?

Research shows that clonidine, a drug that reduces norepinephrine (a stress-related chemical) levels, helped 72% of veterans with PTSD improve their symptoms, with 49% experiencing significant improvement. It is also noted for reducing nighttime PTSD symptoms, including nightmares. ^{1 2 3 4 5}

Is low-dose clonidine safe for humans?

Clonidine has been used safely in humans for many years, primarily as a treatment for high blood pressure. In studies, most people tolerate it well, with common side effects like sedation (feeling sleepy) and dry mouth, which are usually mild and related to the dose. In a study of veterans with PTSD, minimal side effects were reported with low-dose clonidine. ^{1 5 6 7 8}

How does the drug clonidine differ from other treatments for PTSD?

Clonidine is unique in treating PTSD because it works by reducing norepinephrine levels, which are linked to symptoms like hyperarousal and sleep disturbances. Unlike some other treatments, clonidine is an alpha2-adrenergic agonist that specifically targets the sympathetic nervous system to help manage these symptoms. ^{1 4 5 8 9}

Research Team

Michael Fendrich, PhD

Principal Investigator

Wake Forest University Health Sciences

Gregory Burek, MD, MS

Principal Investigator

Wake Forest University Health Sciences

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Evaluation of Clonidine and Prazosin for the Treatment of Nighttime Posttraumatic Stress Disorder Symptoms. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Opiate and cocaine dependencies. Techniques to help counter the rising tide. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Clonidine in neuropsychiatric disorders: a review. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Clonidine Use for the Treatment of Nightmares in Posttraumatic Stress Disorder. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Low-dose clonidine in veterans with Posttraumatic stress disorder. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Clonidine hydrochloride. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Comparison of the pharmacokinetics, pharmacodynamics, and safety of oral (Catapres) and transdermal (M-5041T) clonidine in healthy subjects. [2019]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Determination of clonidine in human plasma by cold on-column injection capillary gas chromatography-selected-ion monitoring-mass spectrometry. [2013]

9. England pubmed.ncbi.nlm.nih.gov

Stability of clonidine hydrochloride in an oral powder form compounded for pediatric patients in Japan. [2021]