By:

Ajeigbe Isaac Olaolu, B.Sc., M.B.A.

Parkinson’s Disease Clinical Research Challenges and Best Practices

Humber, Toronto, Canada

2015

Clinical Research Project Supervisor in Specific Diseases

Prof. Peivand Pirouzi

Definition

What is Parkinson’s disease?

What causes PD?

Who gets Parkinson’s disease?

How is Parkinson’s disease diagnosed?

What are the symptoms?

What are treatment options available?

Clinical Trials on Parkinson’s disease

Challenges, Progress and Future approaches

Parkinson’s disease is a chronic, progressive

neurological disease that affects nerve cells

(neurons) in an area of the brain called the

substantia nigra.

These cells normally produce dopamine, a

chemical (neurotransmitter) that transmits signals

between areas in the brain. These signals, when

working normally, coordinate smooth and

balanced muscle movement.

The brain stem called the substantia nigra controls movement.

Parkinson's disease cells in the substantia nigra stop making dopamine

Neurotransmitter helps nerve cells communicate.

As these dopamine-making cells dies due to accumulation of protein alpha-synuclein bound to damaged cell.

The brain does not receive the necessary messages about how and when to move.

The loss of dopamine causes PD symptoms

PD is a progressive disease of the nervous system

marked by tremor, muscular rigidity, and slow, imprecise

movement, chiefly affecting middle-aged and elderly

people.

The primary symptoms of PD are tremor, or trembling in

hands, arms, legs, jaw, and face; rigidity, or stiffness of

the limbs and trunk; bradykinesia, or slowness of

movement; and postural instability, or impaired balance

and coordination.

Incidence of PD has reported higher in men than

woman, especially after the age of 60.

The average age at the onset of symptoms is 61.

Reported that about10 percent of patients are

diagnosed before age 40.

PD may be inherited genetically

Environmental factors associated with risk of

having PD

Environmental exposures to toxins contributes to

having PD

Qualified, trained Neurologist diagnoses PD

Currently no sophisticated blood or laboratory tests

available to diagnose the disease.

Some imaging tests, such as CT (computed

tomography) or MRI (magnetic resonance imaging)

scans, may be used to rule out other disorders that

cause similar symptoms.

A detailed medical history needed. This includes

questions about the patient’s symptoms, medications,

and the possible exposure to toxins

Neurological examination

Use of diagnostic criteria especially in the early stages

PD affects movement, producing motor symptoms and non-motor signs.

Common motor symptoms includes tremor (confined to a body part), rigidity of muscles or stiffness of limbs, bradykinesia (slowness of movement) and postural instability.

Less common non-motor symptoms includes neuropsychiatric problems like mood, cognition, behaviour or thought alterations, sensory and sleep difficulties, constipation and skin problems

Others may include speech changes, handwriting changes, pain, apathy, fatigue, impaired color discrimination and restless leg syndrome.

Hoehn and Yahr Staging of Parkinson’s DiseaseStage 1:

. Signs and symptoms on one side only

. Symptoms mild

. Symptoms inconvenience but not disabling

. Usually presents with tremor of one limb

. Friends have noticed changes in posture, locomotion and facial expression

Stage 2:. Symptoms are bilateral. Minimal disability. Posture and gait affected

Stage 3:. Significant slowing of body movements. Early impairment of equilibrium on walking or standing

Stage four:

◦ . Severe symptoms

◦ . Can still work to a limited extent

◦ . Rigidity and bradykinesia

◦ . No longer able to live alone

◦ . Tremor may be less than earlier stages

Stage five:

. Cannot stand or walk

. Invalidism complete

. Cachectic stage

. Requires constant nursing care

Although there is no cure for PD but medications to relief from symptoms

Two major treatments: Drug treatments and surgery, others are complementary and supportive therapies.

Medication options Levodopa + a dopa decarboxylase inhibitor

(carbidopa) or COMT inhibitor. Dopamine agonist + MAO-B inhibitors (selegiline,

rasagiline) Some COMT inhibitors: tolcapone, entacapone, Some dopamine agonists like ropinirole, pramipexole,

bromocriptine, pergolide, piribedil, cabergoline, apomorphine, lisuride and rotigotine

Others are amantadine and benzotropine

Deep brain stimulation : this involves implantation of medical device called a brain peace maker.

DB Stimulator send electrical impulses to specific part of the brain.

For PD with motor fluctuations and inadequately controlled tremor by medication

Pallidotomy: it involves surgical destruction of the globus pallidus to control dyskinesia

Here lesions are formed to suppress overactivity of specific subcortical areas

. Rehabilitation:

Regular physical exercise help with gait and

voice therapy

. Palliative care:

Specialized medical care for people with

serious illness

. Dietary care:

Balanced diet based on periodic nutritional

assessments

.Caffeine & Nicotine consumption –appears protective

Clinical Trial: NCT00594165

. An Open-Label Extension Trial to Assess the

Safety of Long-Term Treatment of Rotigotine

in Early-Stage Parkinson’s Disease

Clinical Trial: NCT00501969

. An Open-Label Extension Trial to Assess the

Safety of Long-Term Treatment of Rotigotine

in Advanced- Stage Parkinson’s Disease

Purpose:

The objective of this open-label extension is to

assess the safety and tolerability of long-term

treatment of the Rotigotine patch in subjects with

Early Idiopathic Parkinson’s Disease

Study design:

Endpoint classification: Safety/ Efficacy study

Intervention Model: Single group Assignment

Masking: Open Label

Primary purpose: Treatment

Condition: Early-Stage PD

Recruitment Information:

Recruitment status: Completed

Enrollment : 217

Study Start Date : June 2002

Completion Date : November 2008

Eligibility Criteria for Study:

Age Eligible : 31 Years and Above

Gender Eligible : Both

Accept Healthy Volunteers : No

Inclusion Criteria :

Subjects who have completed six months of maintenance treatment in the SP512 double-blind trial

Exclusion Criteria :

Subjects who had an ongoing serious adverse

event from SP512 double-blind trial that was

assessed as related to study medication

Intervention : Drug Rotigotine; Rotigotine trans-

dermal patch 10 cm2 (2 mg/24 hours);

20 cm2 (4 mg/24 hours);

30 cm2 (6 mg/24 hours);

40 cm2 (8 mg/24 hours)

Study Phase : Phase 3

During the first year :

The maximum Rotigotine dose allowed is 6 mg/24

hours.

After the first year : allowed dose increase of

Rotigotine up to a maximum of 16 mg/24 hours.

Primary Outcome Measures :

Number of Subjects With at Least One Adverse

Event During This Open-label Extension Study

[Time Frame: 7 years ]

Secondary Outcome Measures:

Number of Subjects Who Withdrew From the Trial Due to an Adverse Event. [ Time Frame: 7 years ]

Overall Study Results:

Number of Participants analyzed = 216

Number of Subjects with at least one AE =214

Number of subjects who withdrew due to an AE =52

Total Adverse Events in the Study = 206/216 (95.37%)

Total Serious Adverse Events in the study = 102/216 (47.22%)

No cure yet to Parkinson’s disease

Subject withdrawal before the end of trials

Subject unsatisfactory compliance – protocol

violations

Subject enrollment in other trials

Subject moving to other places

Finding the potential cause of PD

Investigating potential new treatments

Finding Global statistical test for diagnosing PD

Environmental factors; Industrialized nations and

exposures to toxins.

Therapeutic Approaches

Drug Therapies

Surgical Therapies

Cell transplants (Stem cells)

Gene therapy

Transcranial Magnetic Stimulation

Deep Brain Stimulation

Genes discoveries

Neuroprotection

Efforts to halting the progression of PD

Restoring lost functions due to PD

Moving towards preventing PD

Improving Rehabilitation and Assertiveness of Technology for PD

Assessing Quality of life of PD patients

On-going studies includes: Studies of Structures and functions of proteins involved in PD;

Studies PD risk factors in people of different gender and ethnicity and Anatomical studies of structures and brain channels involved in PD

https://www.youtube.com/watch?v=aYRCexa5FCk