Posts

SPEAK OUT! Voice Therapy Program Improves Speech in Parkinson’s Patients, Study Shows

SPEAK OUT voice therapy

A voice therapy program called SPEAK OUT!, developed by the Parkinson Voice Project, can help Parkinson’s disease patients regain their ability to communicate, according to a new study.

Parkinson’s patients, especially those who received the training in early stages of the disease, saw improvements in speech intensity, pitch range, reading intelligibility, and vocal quality after SPEAK OUT! therapy.

The study, “Prosodic Improvement in Persons with Parkinson Disease Receiving SPEAK OUT! Voice Therapy,” was published in the journal Folia Phoniatrica et Logopaedica.

Many Parkinson’s patients experience voice dysfunctions and problems in their ability to articulate speech.

Speech deficits are often characterized by reduced loudness, breathy voice, monotone pitch, voice tremor, intermittent rapid rushes of speech, and imprecise production of consonants, which significantly impacts a patient’s ability to communicate.

For many patients, this is just another disease manifestation to which they resign themselves. However, speech impairment can lead to social and emotional isolation, with severe implications in the quality of life of patients.

SPEAK OUT! is an individual speech therapy program of 12 sessions, 45 minutes each, given over four weeks.

Sessions are planned to cover six main vocal activities, including vocal warm-ups, vowel prolongation exercises, intonation/gliding exercises, verbal delivery of automatic sequences, oral reading of sentences or passages, and cognitive tasks.

Participants are also asked to do homework assignments, which include a twice-daily speech exercise for 25 consecutive days.

Researchers at the Motor Speech and Prosody Research Lab at the University of Oklahoma enrolled 16 patients who had Parkinson’s for a mean duration of 7.9 years.

They were evaluated at the INTEGRIS Jim Thorpe Rehabilitation Center in Oklahoma City one to three weeks before and after the voice therapy. During the assessment session, they were asked to read a short text and to speak in a conversational style.

SPEAK OUT! effects were assessed using self-reported questionnaires — Voice Handicap Index (VHI) and Voice-related Quality of Life (V-ROL) questionnaires — and by a clinically certified speech-language specialist who rated the ability of patients to articulate their speech.

The voice program brought benefits to patients, who reported an average improvement in their VHI and V-ROL questionnaires scores of 21 and 6 points, respectively. This represented a change from severe to mild speech impairment after therapy.

Clinical assessment also showed significant improvements in reading intonation and intelligibility. Also, participants were able to use fewer monotone sounds and less whispery voices after receiving the therapy. This evaluation also confirmed a significant improvement in overall speech impairment.

These findings suggest that “while Parkinson’s disease is progressive and degenerative in nature, speech impairments associated with the disease respond favorably to rehabilitation,” the researchers wrote.

But because the voice therapy is more effective in patients who had Parkinson’s for a shorter amount of time, researchers suggest that SPEAK OUT! should be administered as early as possible after disease onset.

The post SPEAK OUT! Voice Therapy Program Improves Speech in Parkinson’s Patients, Study Shows appeared first on Parkinson’s News Today.

Source: Parkinson's News Today

Better Understanding of Parkinson’s Psychosis Needed to Develop New Therapies, Study Suggests

psychosis

Improved understanding of Parkinson’s disease psychosis (PDP) and a unified approach for its clinical evaluation are key for developing new therapeutics, a review study suggests.

The research, “Treating Hallucinations and Delusions Associated With Parkinson’s Disease Psychosis,” was published in the journal Current Psychiatry Reports.

PDP has been increasingly recognized as a distinct clinical symptom linked with Parkinson’s progression, dementia, and medications. Both its diagnosis and symptom management remain challenging.

PDP is a non-motor symptom that causes patients to experience hallucinations and delusions, with more than half of Parkinson’s patients developing psychosis over the course of their disease.

PDP involves diverse neurotransmitter systems. Altered functioning of serotonin 5-HT2A receptors may affect how PDP patients process what they see.

Visual hallucinations — seeing, hearing, or feeling things that do not exist — are the most frequent feature in PDP patients, but non-visual hallucinations also may occur. Delusions  — distorted interpretations of reality — are more often paranoid and related to persecution or infidelity.

Both visual hallucinations and delusions are risk factors for nursing home placement, which has been associated with a 100 percent mortality rate in a two-year follow-up study. This underscores “the severity with which psychosis correlates with the disease state,” authors wrote. PDP also may impact caregivers, who have shown greater risks for chronic illnesses, depression, and mortality.

As for risk factors underlying the development of psychotic symptoms, dementia and cognitive impairment have been demonstrated extensively. Older age, Parkinson’s duration and severity, and sleep disturbances also are associated with greater risk of PDP.

Regarding treatment, non-pharmacological approaches are an important initial option. Potential reversible medical problems and patients’ non-Parkinson’s related medications — in particular antidepressants, sedatives, and narcotics — should be assessed carefully. Clinicians should then focus on Parkinsonian medications with the greatest risk of inducing psychosis, and always be on the lookout for worsening of motor symptoms.

Regarding pharmacological options, until recently patients had no approved treatments, leading to off-label use of atypical antipsychotics, which may worsen motor symptoms. These medications differ from typical antipsychotics because they induce fewer extrapyramidal symptoms, which are drug-induced movement disorders that include acute and late symptoms.

Pharmacological approaches should be considered if non-pharmacologic strategies and reducing doses of anti-parkinsonian medications are not able to reduce PDP symptoms without affecting motor function, the authors noted.

Several studies demonstrated the safety and tolerability of low-dose Clozaril (clozapine, HLS Therapeutics), an atypical antipsychotic, in PDP patients, without worsening their motor symptoms. Supporting research included multi-center, double-blind trials, which reported benefits with doses ranging between 6.25–50 mg/day. However, patients’ white blood cell counts should be monitored.

Seroquel (quetiapine, AstraZeneca) is a more potent blocker of 5-HT2A receptors than Clozaril. Studies found better results with lower doses, but lack of superior effectiveness over placebo has been consistent.

Zyprexa (olanzapine), which has higher affinity for 5-HT2A receptors than for dopaminergic D2 receptors, showed effective reduction of psychosis, but several studies showed worsened motor function, while others failed to observe differences compared to placebo. As a result, the American Academy of Neurology concluded that olanzapine should not be routinely used for PDP.

More recently, Acadia Pharmaceuticals developed Nuplazid (pimavanserin), a selective 5-HT2A/C receptor inverse agonist with no activity on dopamine receptors, which is an important feature given Parkinson’s patients’ loss of dopaminergic neurons. Inverse agonists induce pharmacological responses opposite to agonists though binding to the same receptors. Doses between 25 and 60 mg/day showed good safety and tolerability results without worsening motor symptoms.

In a larger Phase 3 clinical trial with 199 patients taking either Nuplazid 40 mg/day or placebo over six weeks, the therapy improved both sensory hallucinations and delusions, improved sleep and cognition, and did not lead to declined motor function. Nuplazid became the first medication approved by the U.S. Food and Drug Administration to treat PDP.

Several other atypical antipsychotics and non-antipsychotic medications have been assessed for PDP, but their variable effectiveness and potential motor-worsening falls short of a recommendation for standard use. These include risperidone, ziprasidone, aripiprazole, and melperone.

“While new therapeutics and targets continue to be investigated, a more complete understanding of PDP pathology is needed to further refine drug targets,” the researchers wrote.

“Ultimately, investigation into novel agents will require exploration of not only selective receptor targets, but also a unified approach to the clinical evaluation of PDP itself,” they added.

The post Better Understanding of Parkinson’s Psychosis Needed to Develop New Therapies, Study Suggests appeared first on Parkinson’s News Today.

Source: Parkinson's News Today

#AAN2018- Inbrija Reduces Parkinson’s Off Periods, Phase 3 Trial Shows

Phase 3 Inbrija trial

Inbrija reduces Parkinson’s symptoms when standard treatments wear off, and decreases the length of these off periods, a Phase 3 clinical trial shows.

The therapy’s developer, Acorda Therapeutics, will present the results at the American Academy of Neurology annual meeting in Los Angeles, April 21-27. Parkinson’s News Today will be covering the conference.

Acorda’s presentation will be at 4:54 p.m. Pacific time on Tuesday, April 24. The title will be “Long-term Efficacy of Inhaled Levodopa in Parkinson’s Disease Subjects With Motor Fluctuations: a Phase 3 Open-Label Randomized Study.”

Inbrija (CVT-301) is a self-administered, inhaled version of levodopa intended to reduce the time when standard levodopa treatment wears off — periods known as off times.

Acorda conducted the Phase 3 trial (NCT02352363) to evaluate the safety and effectiveness of an 84-mg dose of Inbrija over 12 months in 408 Parkinson’s patients with movement problems.

The Inbrija group consisted of 278 patients. The other 130 were assigned to standard care. Only 204 of the patients who received Inbrija were able to complete the trial.

At the beginning of the study, the Inbrija group had a mean age of 63.6 years, had had Parkinson’s for nine years, were averaging 3.6 off periods a day, and were experiencing total off times of 5.6 hours per day. Patients took an average of 2.3 doses of Inbrija a day.

One of the measures that researchers used to measure Inbrija’s effectiveness was improvements in patients’ UPDRS-III scores, which assess both movement and non-movement symptoms, 10, 20, 30, and 60 minutes after dosing. Another measure was the percentage of patients able to regain control of their symptoms within 60 minutes of treatment.

Still another measure was reductions in patients’ off times. And a fourth was better scores on a scale known as PGIC, which shows whether a patient believes a treatment is effective.

A key finding was improvements in Parkinson’s symptoms at all time points between week 4 and 52 on the UPDRS-III scale.

Another finding was that patients were able to regain control of their symptoms within 60 minutes.

In addition, patients were able to reduced their total daily off times by between 1.32 and 1.42 hours. And 75 percent of patients showed improvements in PGIC scores.

Overall, improvements in UPDRS-III scores, daily off times and PGIC scores “support the efficacy of up to 52 weeks of treatment with CVT-301 (Inbrija) 84 mg in the treatment of off period symptoms,” the researchers wrote.

The results prompted Acorda to seek European Union approval of Inbrija as a treatment for off periods in Parkinson’s.

In addition to data from this Phase 3 trial, Acorda’s application to the EU included results of the Phase 3 SPAN-PD trial (NCT02240030) in 351 participants and the Phase 3 CVT-301-004E trial (NCT02242487) in 325 participants.

The U.S. Food and Drug Administration accepted Acorda’s New Drug Application for Inbrija in February 2018. It is expected to decide whether to approve it by October 5.

The post #AAN2018- Inbrija Reduces Parkinson’s Off Periods, Phase 3 Trial Shows appeared first on Parkinson’s News Today.

Source: Parkinson's News Today

Acorda Asks European Union to Approve Inbrija for Parkinson’s Off Periods

Inbrija approval request

Acorda Therapeutics has asked the European Medicines Agency to approve Inbrija (CVT-301) to reduce the periods when the standard Parkinson’s treatment carbidopa/levodopa is not working.

Inbrija is a self-administered, inhaled levodopa therapy. Acorda developed it to reduce the time when standard levodopa treatment wears off — periods known as off times.

Both movement and non-movement symptoms return during off times. About half of  patients taking standard levodopa have off periods, which become more frequent and severe during the course of the disease.

Inbrija was designed to deliver a precise dose of a dry powder form of levodopa to patients’ brains. The powder form bypasses the digestive system, preventing delays in the medication kicking in.

Acorda filed a marketing authorization application asking the European Union to approve the therapy. The application included results from its 12-week Phase 3 SPAN-PD clinical trial (NCT02240030). The study assessed the safety and effectiveness of 84-mg and 60-mg doses of Inbrija’s administered up to five times a day in 351 Parkinson’s patients experiencing off periods.

Inbrija improved patients’ movement in comparison with a placebo, results showed.

In line with a previous Phase 2b trial, researchers found no lung safety concerns. The most common adverse events were cough, upper respiratory tract infection, and throat irritation.

Acorda presented the SPAN-PD results at the International Congress of Parkinson’s Disease and Movement Disorders in Vancouver, Canada, in June 2017.

The application included the results of two long-term Phase 3 safety trials as well. The CVT-301-005 trial (NCT02352363) covered 408 patients, and the CVT-301-004E study (NCT02242487) 325 participants.

Researchers found no changes in the treated patients’ lung function, compared with standard levodopa treatment. Taken together, the findings indicated that Inbrija was safe as an off-period treatment, Acorda said.

The U.S. Food and Drug Administration accepted Acorda’s New Drug Application for Inbrija in February 2018. It expects to decide by October 5 whether to approve it.

U.S. regulators refused to accept Acord’s initial application due to concerns over the manufacturing of Inbrija. The company addressed the questions in a revised application.

Acorda’s European application covers all European Union countries, as well as Norway, Liechtenstein, and Iceland.

The post Acorda Asks European Union to Approve Inbrija for Parkinson’s Off Periods appeared first on Parkinson’s News Today.

Source: Parkinson's News Today