Propranolol for Primary Progressive Aphasia

Overseen By Jessica Call

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Missouri-Columbia

Must not be taking: Alpha 2 agonists

Disqualifiers: Diabetes, Reactive airway disease, others

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

Compensation: Varies

Number of Visits: 1

Duration: 18 weeks

30 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to find out how the language of people with Primary Progressive Aphasia is affected by Propranolol. Propranolol is not FDA approved for the treatment of Primary Progressive Aphasia. Propranolol is FDA approved for the treatment of heart conditions such as blood pressure. This research is being done because there are currently no drug treatment options for language impairments and anxiety often experienced by people with Primary Progressive Aphasia.

Will I have to stop taking my current medications?

The trial requires that you stop taking alpha 2 agonists (like clonidine and guanfacine) and any drugs that interact with propranolol. If you're on these medications, you would need to stop them to participate.

Is the drug propranolol effective for treating primary progressive aphasia?

There is no direct evidence supporting the use of propranolol for primary progressive aphasia, but it has shown effectiveness in reducing symptoms in other conditions like migraines and behavioral issues in dementia, suggesting it might have potential benefits in managing certain symptoms. ^{1 2 3 4 5}

Is propranolol generally safe for humans?

Propranolol is generally considered safe for humans, but it can cause side effects. In one case, it was associated with psychotic symptoms like hallucinations, which resolved when the medication was stopped. ^{1 3 6 7 8}

What makes the drug Propranolol unique for treating Primary Progressive Aphasia?

Propranolol is unique for treating Primary Progressive Aphasia because it is a beta-blocker typically used for heart-related conditions, and there are no standard treatments specifically for this condition, making its use novel in this context. ^{9 10 11 12 13}

Research Team

David Beversdorf, MD

Principal Investigator

University of Missouri-Columbia

Eligibility Criteria

This trial is for individuals aged 50 or older who have been diagnosed with Primary Progressive Aphasia and are native English speakers. It's not suitable for those with major head trauma, untreated hypothyroidism, certain heart conditions like bradyarrhythmia, unexplained fainting episodes, diabetes, reactive airway diseases or those on conflicting medications.

Inclusion Criteria

I am 50 years old or older.

I am a native English speaker.

I have been diagnosed with Primary Progressive Aphasia.

Exclusion Criteria

You are pregnant.

I am unable to give my consent.

I am currently taking clonidine or guanfacine.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive propranolol or placebo via oral capsule, with dosage titration for propranolol

18 weeks

Visits at Day 1, 4 weeks, 8 weeks, 10 weeks, 14 weeks, 18 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Propranolol

Trial Overview The study tests if Propranolol can improve language abilities in people with Primary Progressive Aphasia. Participants will either receive Propranolol or a placebo (a substance with no therapeutic effect). Their language function will be monitored using MRI scans to observe any changes.

Participant Groups

Group I: Propanolol and MRI Experimental Treatment 2 Interventions

Participants will receive propranolol via oral capsule. The drug dosage will be titrated slowly to ensure the drug is tolerated well.

Group II: Placebo and MRI Placebo Group 2 Interventions

Participants will receive placebo via oral capsule.

Propranolol is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Inderal for:

• High blood pressure
• Angina pectoris
• Heart rhythm disorders
• Migraine prophylaxis
• Essential tremor
• Performance anxiety

Approved in European Union as Propranolol for:

• Hypertension
• Angina pectoris
• Arrhythmias
• Migraine prophylaxis
• Essential tremor
• Anxiety

Approved in Canada as Propranolol for:

• Hypertension
• Angina pectoris
• Arrhythmias
• Migraine prophylaxis
• Essential tremor
• Anxiety

Who Is Running the Clinical Trial?

University of Missouri-Columbia

Lead Sponsor

Trials

387

Recruited

629,000+

Findings from Research

A study involving six healthy adult volunteers tested four different brands of propranolol (Inderal, Ciplar, Corbeta, and Propal) to assess variations in how the body absorbs and responds to the medication.

The results showed no significant differences in the pharmacokinetic (how the drug is processed in the body) and pharmacodynamic (the drug's effects on the body) parameters among the brands, indicating they are likely interchangeable in terms of efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative pharmacokinetic and pharmacodynamic study of four different brands of propranolol in normal volunteers. Biswas, NR., Garg, SK., Kumar, N., et al.[2013]

In a 10-week study involving 29 patients with mild to moderate hypertension, both conventional propranolol tablets taken twice daily and a long-acting formulation (Inderal LA) taken once daily were found to be equally effective.

Both treatment options were well tolerated, and the once-daily dosage of Inderal LA may improve patient compliance compared to the twice-daily regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of a once daily long-acting formulation of propranolol with conventional propranolol given twice daily in patients with mild to moderate hypertension. Douglas-Jones, AP.[2017]

In a study involving 51 patients, both long-acting formulations of propranolol significantly reduced the frequency of migraine attacks compared to placebo, demonstrating their efficacy in migraine management.

The higher dose formulation (Inderal LA 160 mg) was more effective than the lower dose (Half-Inderal LA 80 mg) in reducing migraine frequency, with no significant difference in side effects between the two formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-acting propranolol in the prophylaxis of migraine: a comparative study of two doses. Carroll, JD., Reidy, M., Savundra, PA., et al.[2017]

Propranolol has shown potential benefits in managing behavioral and psychological symptoms of dementia (BPSD), such as agitation and aggression, based on a review of three case series, one randomized controlled trial, and one case report.

The medication is well tolerated with no significant side effects like bradycardia or hypotension reported, but due to limited data compared to other treatments, it is not routinely recommended for BPSD unless other medications have failed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Propranolol for the management of behavioural and psychological symptoms of dementia. Tampi, RR., Tampi, DJ., Farheen, SA., et al.[2022]

In a study involving twelve chronic schizophrenic patients, high doses of propranolol (1,280-1,920 mg per day) showed a significant improvement in psychotic symptoms compared to placebo, as measured by the CPRS rating scale.

The results suggest that propranolol may have an antipsychotic effect in some patients already on neuroleptic treatment, with six out of twelve patients experiencing improvement during the two-week propranolol treatment period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Propranolol in chronic schizophrenia: a controlled study in neuroleptic-treated patients. Lindström, LH., Persson, E.[2019]

A 53-year-old male developed severe psychiatric symptoms, including hallucinations and combativeness, after starting treatment for hypertension with propranolol, furosemide, and minoxidil.

Switching from propranolol to atenolol led to the complete resolution of the psychotic symptoms, suggesting that propranolol may have contributed to the neuropsychiatric side effects in this patient.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Propranolol-induced psychosis. McGahan, DJ., Wojslaw, A., Prasad, V., et al.[2019]

Controlled-release formulations of propranolol, specifically Elanol and Inderal LA, provide smoother serum level profiles and delayed peak times compared to conventional propranolol, indicating a potentially more stable therapeutic effect.

Elanol showed greater bioavailability than Inderal LA, suggesting that long-acting formulations can be effective without the drawbacks of reduced bioavailability due to first-pass metabolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic and pharmacodynamic studies with a new controlled-release formulation of propranolol in normal volunteers: a comparison with other commercially available formulations. Perucca, E., Grimaldi, R., Gatti, G., et al.[2019]

In a study involving 20 migraine patients, both Inderal (racemic propranolol) and d-propranolol were found to be significantly more effective than placebo in reducing migraine frequency.

While Inderal appeared to be more effective than d-propranolol, the difference was not statistically significant, suggesting that both beta-blocking and potentially other mechanisms contribute to the anti-migraine effects of propranolol.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-term clinical trial of phopranolol in racemic form (Inderal), D-propranolol and placebo in migraine. Stensrud, P., Sjaastad, O.[2019]

Persons with severe hemophilia A and B are aging and facing similar comorbidities as their peers, including chronic conditions like cancer and cardiovascular disease, which can lead to polypharmacy.

Despite the potential for drug interactions, the rate of polypharmacy and associated risks in aging individuals with hemophilia is relatively low, likely due to coordinated care from specialized hemophilia treatment centers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aging with Hemophilia: The Challenge of Appropriate Drug Prescription. Mannucci, PM.[2020]

A study involving 36 hematologists from the US and Europe revealed that efficacy (35.0%) and scientific evidence (34.1%) are the most important factors for physicians when choosing prophylactic treatments for patients with severe hemophilia A who have developed inhibitors to factor VIII.

Cost, dosing frequency, and administration time were considered less important, indicating that physicians prioritize treatment effectiveness and supporting research over other logistical factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physician preferences for medication attributes for the prophylactic treatment of patients with severe haemophilia A with inhibitors to factor VIII. Gelhorn, H., Merikle, E., Krishnan, S., et al.[2015]

In a study of 17 young adults with severe hemophilia A on a low-dose daily prophylaxis (LDDP) regimen, participants maintained a high adherence rate of 84% and experienced low annualized bleeding rates, indicating that LDDP can be an effective treatment option.

The study found that the health-related quality of life (HRQoL) scores remained stable over the 2 to 3 years, suggesting that LDDP not only helps manage bleeding but also supports overall well-being in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adherence to treatment regimen and bleeding rates in a prospective cohort of youth and young adults on low-dose daily prophylaxis for severe hemophilia A. Mizrahi, T., St-Louis, J., Young, NL., et al.[2020]

In a pilot trial involving 57 patients with symptomatic hip osteoarthritis, intra-articular injections of hylan G-F20 were found to be feasible and well-tolerated, with only 10.1% of injections resulting in transient hip pain and no serious adverse events reported.

Patients experienced a significant reduction in walking pain, decreasing from an average of 69.3 mm to 39.5 mm on a visual analogue scale, indicating that hylan G-F20 may effectively alleviate symptoms of hip osteoarthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intra-articular injections of hylan G-F 20 in patients with symptomatic hip osteoarthritis: an open-label, multicentre, pilot study. Conrozier, T., Bertin, P., Mathieu, P., et al.[2017]

In a study of 313 patients with hip osteoarthritis, hylan G-F 20 showed greater improvement in pain and function compared to methylprednisolone acetate (MPA) at week 26, particularly in patients with more advanced disease (KLG 3).

Both treatments had similar safety profiles, indicating that hylan G-F 20 is a safe and effective alternative to MPA for managing symptoms of hip osteoarthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hylan G-F 20 improves hip osteoarthritis: a prospective, randomized study. Spitzer, AI., Bockow, BI., Brander, VA., et al.[2018]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Comparative pharmacokinetic and pharmacodynamic study of four different brands of propranolol in normal volunteers. [2013]

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

Comparison of a once daily long-acting formulation of propranolol with conventional propranolol given twice daily in patients with mild to moderate hypertension. [2017]

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

Long-acting propranolol in the prophylaxis of migraine: a comparative study of two doses. [2017]

4. England pubmed.ncbi.nlm.nih.gov

Propranolol for the management of behavioural and psychological symptoms of dementia. [2022]

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

Propranolol in chronic schizophrenia: a controlled study in neuroleptic-treated patients. [2019]

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

Propranolol-induced psychosis. [2019]

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

Pharmacokinetic and pharmacodynamic studies with a new controlled-release formulation of propranolol in normal volunteers: a comparison with other commercially available formulations. [2019]

8. Denmark pubmed.ncbi.nlm.nih.gov

Short-term clinical trial of phopranolol in racemic form (Inderal), D-propranolol and placebo in migraine. [2019]

9. Italy pubmed.ncbi.nlm.nih.gov

Aging with Hemophilia: The Challenge of Appropriate Drug Prescription. [2020]

10. England pubmed.ncbi.nlm.nih.gov

Physician preferences for medication attributes for the prophylactic treatment of patients with severe haemophilia A with inhibitors to factor VIII. [2015]

11. England pubmed.ncbi.nlm.nih.gov

Adherence to treatment regimen and bleeding rates in a prospective cohort of youth and young adults on low-dose daily prophylaxis for severe hemophilia A. [2020]

12. Italy pubmed.ncbi.nlm.nih.gov

Intra-articular injections of hylan G-F 20 in patients with symptomatic hip osteoarthritis: an open-label, multicentre, pilot study. [2017]

13. England pubmed.ncbi.nlm.nih.gov

Hylan G-F 20 improves hip osteoarthritis: a prospective, randomized study. [2018]