Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04858074 |
| Other study ID # |
UI/EC/20/0320 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 1/Phase 2
|
| First received |
|
| Last updated |
|
| Start date |
January 3, 2022 |
| Est. completion date |
December 31, 2022 |
Study information
| Verified date |
May 2023 |
| Source |
University of Ibadan |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Parkinson's disease (PD) is a progressive neurological disease characterized by resting
tremors, limb stiffness, impaired balance, and slow movement. There is no known cure for PD
although levo-3,4 dihydroxyphenylalanine (L-DOPA) and dopamine agonists are effective for
improving PD symptoms in the early years following diagnosis. Hypoestes rosea is an evergreen
shrub which has anti-inflammatory, anticancer and antimalarial properties. Recent studies
showed that the active pharmaceutical ingredient (API) of Hypoestes rosea, Hypoestoxide, was
effective in modifying disease progression in a transgenic mouse model of PD.
The aim of this study is to determine the efficacy of Hypoestoxide, as contained in Hypoestes
rosea dry leaf powder, in improving motor symptoms in consenting PD patients. The study
design is a double-blind, placebo-controlled cross-over trial involving 30 patients with mild
to moderate disease (Stages 1-3 of Hoehn and Yahr scale over an 8-week period. The symptoms
of the participants will be monitored using mobile phones with an established quantitative
assessment tool, mPower2.0, which was previously developed for monitoring symptoms and
disease progression in PD patients. In addition, the motor examination component of the
International Movement Disorders Society scale will be administered and correlated with the
finding on the mobile phone. The outcome measure is an improvement in the motor variables of
the study participants with a 10% change from baseline over the 8 weeks of using Hypoestes.
Description:
Justification Age-associated disorders are increasing in many low- and middle-income
countries due to population ageing and changing lifestyles. PD is a devastating condition
which, in the advanced stages, is associated with immobility and uncontrollable tremors. Life
then becomes miserable for the sufferers. Unfortunately, there is no cure for the disease
except control of symptoms with medications. Any treatment combination that leads to better
symptom control will go a long way in improving the quality of life for PD patients. This
proof-of-concept study (POC), if successful will give a new lease on life to PD patients.
Hence it is considered worthwhile to treat PD patients with a new compound that is contained
in a local plant that is readily available and holds promise for efficacy based on its mode
of action specifically in reducing the formation of alpha synuclein which underlies the
neuronal death in PD.
OBJECTIVES OF THE STUDY
The aim of this study is to determine the efficacy of Hypoestoxide, as contained in Hypoestes
rosea dry leaf powder (PECKO-D), in improving motor symptoms in consenting PD patients over
an 8-week period.
Specific Objectives:
• To determine the efficacy of Hypoestes rosea in improving motor performance of PD patients
through traditional clinical evaluation, use of the selected components of the Motor
Examination section of the International Movement Disorders Society Scale and ActiGraph
wearable as a quantitative assessment tool.
- To document the side effect profile of the herbal product
Methodology Study site: University College Hospital, Ibadan Study design: Single-center,
randomized, double-blind, placebo-controlled trial Study Type: Interventional (Clinical
Trial) Allocation: Randomized Masking: Double Primary Purpose: Treatment Study participants:
Patients with mild to moderate Parkinson's disease symptoms.
Eligibility Criteria Ages eligible for study: 30 years and older (Adult, older adult) Sexes
Eligible for Study: All Accepts healthy volunteers: No Sample size: Being a proof-of-concept
study, 19 PD patients will participate in this phase of the study
Inclusion criteria:
• Willing and able to give informed consent.
- Willingness and ability to comply with study requirements.
- PD diagnosis must be confirmed by bradykinesia plus one of the other cardinal signs
(resting tremor, rigidity, postural instability) being present.
- Age >30 years
- Men and women with mild to moderate PD: Hoehn and Yahr scale stages 1 - 3. Participants
may be on current therapeutic agents (including levodopa, dopamine agonists,
anticholinergics, amantadine or selegiline) to treat PD symptoms at the time of
enrollment and may remain on these agents throughout the 5-month study period.
- Women of childbearing potential (i.e., those not postmenopausal or surgically sterile)
may participate provided that they are using adequate birth control methods for the
duration of the study. Women of childbearing potential must have a negative pregnancy
test at baseline and be non-lactating.
Exclusion:
- Subjects with advanced, severe disease, including those with dementia, severe
osteoarthritis, allergies, stroke, and visual impairment.
- Presence of atypical PD syndromes due to drugs (e.g., metoclopramide, flunarizine),
metabolic identified neurogenetic disorders (e.g., Wilson's disease), encephalitis, or
other degenerative diseases (e.g., progressive supranuclear palsy).
- Any clinically significant medical condition (e.g., active neoplasm, angina) or
laboratory abnormality, which would in the judgement of the investigator interfere with
the subjects' ability to participate in the study or be followed.
Study Procedure:
In this study, participants with mild to moderate PD, whether treated or untreated, will be
randomized into one of two study arms following an initial baseline assessment to determine
motor activity status of each participant as follows:
Baseline Determination: Measurement of motor activities of all participants will be
determined for 3 weeks while on regular PD medication(s). The International Movement
Disorders Society Scale - Motor Examination (10 selected items on Slowness, Posture, Tremor,
Rigidity and Gait) will be utilized for the quantitation of the motor activities.
Drug arm: 15 patients will receive 4 capsules each containing 350 mg orally twice a day of
PECKO-D Forte for 8 weeks as add-on therapy to patients' regular PD medication(s).
Placebo arm: 15 participants will receive 4 capsules orally twice a day of United States
Pharmacopeia (USP)-grade starch for 8 weeks as add-on to regular PD medication(s).
Wash-Out: Wash-out will be for a duration of 4 weeks in which patients assigned to both arms
will take no capsules.
The Switch over: Following the wash-out period, the PECKO-D Forte group will receive 4
capsules of USP-grade starch powder taken orally twice a day for 8 weeks. The placebo group
will receive 4 capsules of PECKO-D forte taken orally twice a day for 8 weeks.
Symptoms of the participants will be monitored using traditional clinical evaluation and
daily using ActiGraph as an established quantitative assessment tool Once enrolled and given
the ActiGraph kit, the participants will be asked to perform four (4) separate study tasks
daily during the baseline determination period and throughout the treatment period: gait,
tremor, tapping and balance. The International Movement Disorders Society Scale (MDS) - Motor
Examination (10 selected items on Slowness, Posture, Tremor, Rigidity and Gait) will be
utilized for the quantitation of the motor activities. Data collected using the ActiGraph
will be computer-analyzed and the MDS - Motor items will then be analyzed for significant
changes in symptom severity relative to baseline status.
Measurements:
These include compliance, gait and balance measures before, during, and after treatment with
PECKO-D. Participants will remain on their standard of care PD medications throughout the POC
study and possible adverse side effects of the PEKO-D will be monitored.
The following variables will be documented for each of these key measures:
i) Compliance: hours of device worn per day hours of device wear compliance per week hours of
device worn per treatment period hours of device worn over the course of the study
ii) Gait measures:
start time of walking period in milliseconds end time of walking period in milliseconds
Duration of walking period in seconds Distance walked per walking period in meters Average
gait speed per walking period in meters Number of steps per walking period Average stride
period per walking period in seconds Freeze index per walking period
iii) Balance measures per detected walking period:
- X (lateral) axis variability in g
- Y (forward) axis variability in g
- Z (vertical) axis variability in g
- X-Y (horizontal) variability in g
- Freeze Index (ratio)
OUTCOME MEASURE: 10% Mean change in motor assessment parameters using the International
Movement Disorders Society Scale - selected motor examination items while on the Hypoestes.
This equates to 1- to 2-point improvement in motor performance over a 2-month period on
Hypoestes in the absence of side effects which will be monitored using pharmacovigilance
tools.
Total duration of study: 5 months (2 months on active drugs, 2 months on placebo with one
month wash-out period in-between)
The protocol for the study:
PROOF OF CONCEPT STUDY: to investigate the effect of PECKO-D Forte (100% Hypoestes rosea
powder) in Parkinson's Disease using ActiGraph GT9X wearable as a quantitative assessment
tool
Study Protocol
Serial Number: Hospital Number:
1. Name:
2. Address:
3. Phone number:
4. Gender: Male Female
5. Age (in years) Date of Birth (if known):
CLINICAL DETAILS:
6. Age at diagnosis of PD:
7. DURATION OF DISEASE AT DIAGNOSIS
8. What are the predominant symptoms? (check all that apply) I) Tremor _______ ii)
Stiffness _______iii) Slowness ______iv) Postural instability_______
9. Stage of the disease (from Hoehn and Yahr Scale): _______________ I Unilateral disease
only II Bilateral mild disease III Bilateral disease + early impairment of postural
stability IV Severe disease requiring considerable assistance V Confinement to
wheelchair or bed unless aided
10. Medical co-morbidities i) Hypertension --------- ii) Diabetes Mellitus________ iii)
Heart failure_______iv) Chronic lung disease_________ v) Osteoarthritis _______vi)
Glaucoma______ VII) Others_________________________
11. Current medications and dosages:
I) L-Dopa + carbidopa ii) Anticholinesterase iii) DOPA-agonists (specify) iv) Others
(specify)
12. Medication Side effects (if any)
13. Any major disability experienced - Yes No IF yes, check whichever is applicable:
Cognitive ______ On and off phenomenon_____ Neuropathic pain_________
Dyskinesia____________ others______________
WILLINGNESS TO PARTICIPATE IN STUDY: Yes No
PECKO-D Study
Objective assessment of motor and non-motor- features in PD patients
The MDS-sponsored Revision of the Unified Parkinson's Disease Rating Scale
1. Posture: Instructions to examiner: Posture is assessed with the patient standing erect
after arising from a chair, during walking, and while being tested for postural reflexes. If
you notice poor posture, tell the patient to stand up straight and see if the posture
improves (see option 2 below). Rate the worst posture seen in these three observation points.
Observe for flexion and side-to-side leaning.
0: Normal: No problems.
1. Slight: Not quite erect, but posture could be normal for older person.
2. Mild: Definite flexion, scoliosis or leaning to one side, but patient can correct
posture to normal posture when asked to do so.
3. Moderate: Stooped posture, scoliosis or leaning to one side that cannot be corrected
volitionally to a normal posture by the patient.
4. Severe: Flexion, scoliosis or leaning with extreme abnormality of posture.
2. Global spontaneity of movement (body bradykinesia) Instructions to examiner: This global
rating combines all observations on slowness, hesitancy, and small amplitude and poverty of
movement in general, including a reduction of gesturing and of crossing the legs. This
assessment is based on the examiner's global impression after observing for spontaneous
gestures while sitting, and the nature of arising and walking.
0: Normal: No problems.
1. Slight: Slight global slowness and poverty of spontaneous movements.
2. Mild: Mild global slowness and poverty of spontaneous movements.
3. Moderate: Moderate global slowness and poverty of spontaneous movements.
4. Severe: Severe global slowness and poverty of spontaneous movements.
3. Rigidity: Instructions to examiner: Rigidity is judged on slow passive movement of major
joints with the patient in a relaxed position and the examiner manipulating the limbs and
neck. First, test without an activation maneuver. Test and rate neck and each limb
separately. For arms, test the wrist and elbow joints simultaneously. For legs, test the hip
and knee joints simultaneously. If no rigidity is detected, use an activation maneuver such
as tapping fingers, fist opening/closing, or heel tapping in a limb not being tested. Explain
to the patient to go as limp as possible as you test for rigidity.
0: Normal: No rigidity.
1. Slight: Rigidity only detected with activation maneuver.
2. Mild: Rigidity detected without the activation maneuver, but full range of motion is
easily achieved.
3. Moderate: Rigidity detected without the activation maneuver; full range of motion is
achieved with effort.
4. Severe: Rigidity detected without the activation maneuver and full range of motion not
achieved.
4. Finger tapping: Instructions to examiner: Each hand is tested separately. Demonstrate the
task, but do not continue to perform the task while the patient is being tested. Instruct the
patient to tap the index finger on the thumb 10 times as quickly AND as big as possible. Rate
each side separately, evaluating speed, amplitude, hesitations, halts, and decrementing
amplitude.
0: Normal: No problems.
1. Slight: Any of the following: a) the regular rhythm is broken with one or two
interruptions or hesitations of the tapping movement; b) slight slowing; c) the
amplitude decrements near the end of the 10 taps.
2. Mild: Any of the following: a) 3 to 5 interruptions during tapping; b) mild slowing; c)
the amplitude decrements midway in the 10-tap sequence.
3. Moderate: Any of the following: a) more than 5 interruptions during tapping or at least
one longer arrest (freeze) in ongoing movement; b) moderate slowing; c) the amplitude
decrements starting after the 1st tap.
4. Severe: Cannot or can only barely perform the task because of slowing, interruptions, or
decrements.
5. Toe tapping Instructions to examiner: Have the patient sit in a straight-backed chair with
arms, both feet on the floor. Test each foot separately. Demonstrate the task, but do not
continue to perform the task while the patient is being tested. Instruct the patient to place
the heel on the ground in a comfortable position and then tap the toes 10 times as big and as
fast as possible. Rate each side separately, evaluating speed, amplitude, hesitations, halts,
and decrementing amplitude.
0: Normal: No problems.
1. Slight: Any of the following: a) the regular rhythm is broken with one or two
interruptions or hesitations of the tapping movement; b) slight slowing; c) amplitude
decrements near the end of the ten taps.
2. Mild: Any of the following: a) 3 to 5 interruptions during the tapping movements; b)
mild slowing; c) amplitude decrements midway in the task.
3. Moderate: Any of the following: a) more than 5 interruptions during the tapping
movements or at least one longer arrest (freeze) in ongoing movement; b) moderate
slowing; c) amplitude decrements after the 1st tap.
4. Severe: Cannot or can only barely perform the task because of slowing, interruptions or
decrements.
6. Arising from a chair Instructions to examiner: Have the patient sit in a straight-backed
chair with arms, with both feet on the floor and sitting back in the chair (if the patient is
not too short). Ask the patient to cross his/her arms across the chest and then to stand up.
If the patient is not successful, repeat this attempt up to a maximum of two more times. If
still unsuccessful, allow the patient to move forward in the chair to arise with arms folded
across the chest. Allow only one attempt in this situation. If unsuccessful, allow the
patient to push off using his/her hands on the arms of the chair. Allow a maximum of three
trials of pushing off. If still not successful, assist the patient to arise. After the
patient stands up, observe the posture.
0: Normal: No problems. Able to arise quickly without hesitation.
1. Slight: Arising is slower than normal; or may need more than one attempt; or may need to
move forward in the chair to arise. No need to use the arms of the chair.
2. Mild: Pushes self up from the arms of the chair without difficulty.
3. Moderate: Needs to push off but tends to fall back; or may have to try more than one
time using the arms of the chair but can get up without help.
4. Severe: Unable to arise without help.
7. Gait Instructions to examiner: Testing gait is best performed by having the patient
walking away from and towards the examiner so that both right and left sides of the body can
be easily observed simultaneously. The patient should walk at least 10 meters (30 feet), then
turn around and return to the examiner. This item measures multiple behaviors: stride
amplitude, stride speed, height of foot lift, heel strike during walking, turning, and arm
swing, but not freezing. Observe posture for item 1
0: Normal: No problems.
1. Slight: Independent walking with minor gait impairment.
2. Mild: Independent walking but with substantial gait impairment.
3. Moderate: Requires an assistance device for safe walking (walking stick, walker) but not
a person.
4. Severe: Cannot walk at all or only with another person's assistance.
8. Postural Stability Instructions to examiner: The test examines the response to sudden body
displacement produced by a quick, forceful pull on the shoulders while the patient is
standing erect with eyes open and feet comfortably apart and parallel to each other. Test
retropulsion. Stand behind the patient and instruct the patient on what is about to happen.
Explain that s/he is allowed to take a step backwards to avoid falling. There should be a
solid wall behind the examiner, at least 1-2 meters away to allow for the observation of the
number of retropulsive steps. The first pull is an instructional demonstration and is
purposely milder and not rated. The second time the shoulders are pulled briskly and
forcefully towards the examiner with enough force to displace the center of gravity so that
patient MUST take a step backwards. The examiner needs to be ready to catch the patient but
must stand sufficiently back so as to allow enough room for the patient to take several steps
to recover independently. Do not allow the patient to flex the body abnormally forward in
anticipation of the pull. Observe for the number of steps backwards or falling. Up to and
including two steps for recovery is considered normal, so abnormal ratings begin with three
steps. If the patient fails to understand the test, the examiner can repeat the test so that
the rating is based on an assessment that the examiner feels reflects the patient's
limitations rather than misunderstanding or lack of preparedness. Observe standing posture.
0: Normal: No problems. Recovers with one or two steps.
1. Slight: 3-5 steps, but subject recovers unaided.
2. Mild: More than 5 steps, but subject recovers unaided.
3. Moderate: Stands safely, but with absence of postural response; falls if not caught by
examiner.
4. Severe: Very unstable, tends to lose balance spontaneously or with just a gentle pull on
the shoulders.
9. Rest tremor amplitude Instructions to examiner: This and the next item have been placed
purposefully at the end of the examination to allow the rater to gather observations on rest
tremor that may appear at any time during the exam, including when quietly sitting, during
walking, and during activities when some body parts are moving but others are at rest. Score
the maximum amplitude that is seen at any time as the final score. Rate only the amplitude
and not the persistence or the intermittency of the tremor.
As part of this rating, the patient should sit quietly in a chair with the hands placed on
the arms of the chair (not in the lap) and the feet comfortably supported on the floor for 10
seconds with no other directives. Rest tremor is assessed separately for all four limbs and
also for the lip/jaw. Rate only the maximum amplitude that is seen at any time as the final
rating. Extremity ratings
0: Normal: No tremor.
1. Slight: < 1 cm in maximal amplitude.
2. Mild: ≥ 1 cm but < 3 cm in maximal amplitude.
3. Moderate: ≥ 3 cm but < 10 cm in maximal amplitude.
4. Severe: ≥ 10 cm in maximal amplitude.
10. Constancy of rest tremor Instructions to examiner: This item receives one rating for all
rest tremor and focuses on the constancy of rest tremor during the examination period when
different body parts are variously at rest. It is rated purposefully at the end of the
examination so that several minutes of information can be coalesced into the rating.
0: Normal: No tremor.
1. Slight: Tremor at rest is present ≤ 25% of the entire examination period.
2. Mild: Tremor at rest is present 26-50% of the entire examination period.
3. Moderate: Tremor at rest is present 51-75% of the entire examination period.
4. Severe: Tremor at rest is present > 75% of the entire examination period.
Total Score: (out of 40)
Additional measures include:
Compliance, Gait and Balancing before, during, and after treatment with PECKO-D.
Participants will remain on their standard of care PD medications throughout the POC
study and possible adverse side effects of the PECKO-D will be monitored.
The following variables will be documented for each of these key measures:
i) Compliance: hours of device worn per day hours of device wear compliance per week
hours of device worn per treatment period hours of device worn over the course of the
study
ii) Gait measures:
start time of walking period in milliseconds end time of walking period in milliseconds
Duration of walking period in seconds Distance walked per walking period in meters
Average gait speed per walking period in meters Number of steps per walking period
Average stride period per walking period in seconds Freeze index per walking period
iii) Balance measures per detected walking period:
- X (lateral) axis variability in g
- Y (forward) axis variability in g
- Z (vertical) axis variability in g
- X-Y (horizontal) variability in g
- Freeze Index (ratio)
Any abnormality on neurological
examination?:---------------------------------------------------------------------------
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Blood Pressure:
Pulse:
Weight:
Randomization:: A. Active medication: B. Placebo
Mobile Phone serial number: __________________
Follow up data:
I) First review at 8 weeks:
Date scheduled and time:
Compliance
Any reported side effects?: ____________________________________________________
Any benefits noted subjectively?__________________________________________________
Other comments: ________________________________________________
Assess motor performance using the MDS Scale- Record the score_______
II) 4-week washout period: (No study medications to be administered)
Any comments________________________________________________
III) Cross-over for 8 weeks with change of study medications (Placebo to active and vice
versa)
Date scheduled and time:
Compliance
Any side effects? ____________________________________________________
Any benefits noted? __________________________________________________
Other comments: ________________________________________________
Assess motor performance using MDS scale: Record the score_______
Study completed: Yes No (If No, give reasons) _____________________
Date completed:
Any comments__________________________________________________________
Name and signature of investigator_____________________________________
Date: ----------------------------
