Mild Cognitive Impairment and Endurance Exercise in Parkinson's Disease

Parkinson Disease Clinical Trial

Official title:

Mild Cognitive Impairment and Endurance Exercise in Parkinson's Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03542474
• Other study ID #: STU00202794
• Status: Completed
• Phase: N/A
• Start date: May 15, 2017
• Est. completion date: August 31, 2019

Study information

• Verified date: June 2020
• Source: Northwestern University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The overall objective of this study is to determine how high intensity endurance exercise affects both cognition and the signs and symptoms of Parkinson's disease as well as if certain brain structures and functions also change with this exercise.

Description:

The overall purpose and objective of this project is to test the hypothesis that high intensity endurance exercise causes beneficial brain adaptation in patients with mild cognitive impairment in Parkinson's disease (PD-MCI). Aim 1 will determine the effect of high intensity endurance exercise on cognitive function and other clinical symptoms in PD-MCI. Aim 2 will determine the effect of high intensity endurance exercise on brain structure and function in PD-MCI. Aim 3 will determine the effect of high intensity endurance exercise on cortisol in PD-MCI. Aim 4 will determine the effect of high intensity endurance exercise on inflammation-related biomarkers found in blood in PD-MCI. Aim 5 will determine the effect of high intensity endurance exercise on peripheral levels of neurotrophic factors found in blood in PD-MCI.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: August 31, 2019
• Est. primary completion date: November 5, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 85 Years

Eligibility

Inclusion Criteria:

• Male or female, ages 40-85

• A diagnosis of idiopathic PD

• A diagnosis of PD-MCI

• Due to the stringent head motion during fMRI, we will only include a patient with a head tremor of < 2.

• Hoehn and Yahr stage < or equal to 3

• Stable medication regimen for > or equal to 30 days before entering the study

• Living with a carepartner

Exclusion Criteria:

• PD subjects meeting MDS criteria for PD dementia or having a SCOPA-Cog score less than or equal to 16, or PD subjects having normal cognition defined as a SCOPA-Cog Score of is greater or equal to 25.

• Atypical or secondary parkinsonism as determined by referring Neurologist

• Other disorders that might interfere with ability to perform high intensity endurance exercise (e.g. history of stroke, respiratory problems, traumatic brain injury, known advanced osteoarthritis, or neuromuscular disease).

• Individuals with known injury, disease, or condition that would affect the ability to perform endurance exercise.

• Any other clinically significant medical condition, psychiatric condition, drug or alcohol abuse that would, in the judgment of the investigator, interfere with the subject's ability to participate in the study.

• "Vigorous athletes" participating in any exercise program 2X/week or more will be excluded.

• Individuals with any type of implanted electrical device (such as a cardiac pacemaker or a neurostimulator), or a certain type of metallic clip (i.e., an ° Persons who have had a long history of working in metal shops will be excluded unless they have had a previous orbital x-ray scan clearing them for participation in MRI studies.

• Females who are pregnant or might be pregnant will be excluded from participation.

• Individuals who are claustrophobic and unable to tolerate a brain MRI scan will be excluded.

• Treatment with cholinesterase inhibitors or memantine (i.e., medications approved for treatment of dementia) or medications affecting cognition (i.e., anticholinergics)

• Use of medications that might interfere with neuromuscular junction function such as D-penicillamine and aminoglycoside antibiotics.

• Use of medications that might interfere with the BOLD contrast or heart response to exercise (e.g. ß blockers).

• Individuals at high risk for cardiovascular disease as defined in Table 2.2 by the new ACSM guidelines.(Medicine 2014)

• Younger than 40 and older than 85. We exclude participants younger than 40 because these young onset patients may not be typical of the majority of patients who get the disease later in life. We exclude participants older than 85 because of the limited evidence they can successfully complete a high-intensity endurance exercise program. We also exclude patients whose disease was diagnosed before the age of 40.

• Individuals with known endocrine abnormalities or steroid use that could affect cortisol levels (e.g., Cushing's syndrome, pituitary or adrenal gland disease or adrenalectomy, use of steroid-based medications.

• Individuals with strong history of chronic inflammatory or autoimmune diseases or history of chronic use of NSAIDs, which could cause abnormal levels of inflammatory markers in the plasma.

• We will exclude adults unable to consent, individuals who are not yet adults, pregnant women, prisoners and children from this study.

Related Conditions & MeSH terms

• Cognitive Dysfunction
• Mild Cognitive Impairment
• Parkinson Disease

Intervention

Behavioral:
• High Intensity Endurance Exercise
Treadmill exercise at 80%-85% maximum heart rate for 30 minutes a day, 3 times per week, for 6 months.

Locations

Country	Name	City	State
United States	Northwestern University	Chicago	Illinois

Sponsors (3)

Lead Sponsor	Collaborator
Northwestern University	Rush University Medical Center, Shirley Ryan AbilityLab

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean Change in Cognitive Function	Mean change in cognitive function from baseline to 6-months as measured by global statistical test (GST) for cognitive domains. This will be a composite score reported as Z-scores. The Z-score indicates the number of standard deviations away from the mean, which is based on normative (healthy control) data. A Z-score of 0 is equal to the mean of the normative data with negative numbers indicating values lower than the mean and positive values higher. A positive change in Z-scores indicates a favorable outcome.; The GSTs will be calculated from the following neuropsychological tests administered in the cognitive test battery reflecting specific cognitive domains: Attention/Working Memory - Trail Making Test-Part A; Executive Function - Trail Making Test-Part B, Clock Draw, Raven's Progressive Matrices; Memory - Hopkin Verbal Learning Test-Revised, Free and Cued Selective Reminding Test, Figural Memory Test; Processing Speed - Symbol Digit Modality Test	Baseline and 6 Months
Secondary	6 Month Change in Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Total Score	Mean change in total MDS-UPDRS score. This is a summed total from Part I (non-motor experiences of daily living), Part II (motor experiences of daily living, Part III (motor examination) and Part IV (motor complications). The minimum score on the MDS-UPDRS is 0 and the maximum is 260 with higher scores representing worse symptoms.	Baseline and 6 Months
Secondary	6 Month Change in Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II (Motor Experiences of Daily Living)	Mean change in total MDS-UPDRS Part II (motor experiences of daily living) score. Part II comprises 13 items evaluating the impact of PD on patients' activities of daily living (ADL) over the week prior to the visit such as speech, salivation, swallowing, eating, handwriting, dressing, turning in bed, walking. The total score, being the sum of all these items, can be between 0 to 52. Higher scores represent worse symptoms.	Baseline and 6 Months
Secondary	6 Month Change in Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part I Non Motor Experiences of Daily Living Score	Mean change in total MDS-UPDRS Part I (non-motor experiences of daily living) score. Part I assesses 15 items of non-motor aspects of experiences of daily living. Part IA is assessed by a qualified rater, Part IB is completed by the patient. The total score, being the sum of all these items, can be between 0 to 60. Higher scores represent worse symptoms.	Baseline and 6 Months
Secondary	6 Month Change in Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part IV Motor Complications Score	Mean change in total MDS-UPDRS Part IV (motor complications) score. Part IV assesses motor complications of therapy, such as dyskinesias, motor fluctuations. This part (6 items) is completed by a qualified rater. The total score, being the sum of all these items, can be between 0 to 24. Higher scores represent worse symptoms.	Baseline and 6 Months
Secondary	6 Month Change in Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Motor (Part III) Score	Mean change in total MDS-UPDRS Part III (motor examination) score. The minimum score on the MDS-UPDRS Part III is 0 and the maximum is 132 with higher scores representing worse motor symptoms.	Baseline and 6 Months
Secondary	6 Month Change in Sleep Quality Evaluated by the Epworth Sleepiness Scale (ESS)	The ESS assesses the overall level of daytime sleepiness. Eight items describe normative daily situations known to vary in their soporific qualities. Patients rate the likelihood of dozing off or falling asleep. The test is rated on a 4-point scale (0=would never doze off to 3=high chance of dozing off).	Baseline and 6 Months
Secondary	6 Month Change in Sleep Quality Evaluated by the Pittsburg Sleep Quality Index (PSQI)	The Pittsburgh Sleep Quality Index (PSQI) contains 19 self-rated questions and 5 questions rated by the bed partner or roommate (if one is available). Only self-rated questions are included in the scoring. The 19 self-rated items are combined to form seven "component" scores, each of which has a range of 0-3 points.The global PSQI score is then calculated by totaling the seven component scores, providing an overall score ranging from 0 to 21, where lower scores denote a healthier sleep quality.	Baseline and 6 Months
Secondary	6 Month Change in Fatigue Evaluated by the Fatigue Severity Scale	A 9-item questionnaire with questions related to how fatigue interferes with certain activities and rates its severity according to a self-report scale. The items are scored on a 7 point scale with 1 = strongly disagree and 7= strongly agree. The minimum score = 9 and maximum score possible = 63. Higher the score = greater fatigue severity.	Baseline and 6 Months
Secondary	6 Month Change in Mood Evaluated by the Hamilton Depression Scale (HAM-D)	Although the HAM-D form lists 21 items, the scoring is based on the first 17. Eight items are scored on a 5-point scale, ranging from 0 = not present to 4 = severe. Nine are scored from 0-2. Higher scores represent more severe depression.	Baseline and 6 Months
Secondary	6 Month Change in Quality of Life Evaluated by the Parkinson Disease Neuro Quality of Life (Neuro-QOL)	The NeuroQOL is a self-report of health related quality of life in 17 domains and sub-domains for adults. Item banks consist of 302 items in total (range from 5 to 45) which are used adaptively to test a variable number and content of items in a computer assisted testing format. All items are rated on a five option scale based on intensity (e.g. 1 = not at all, 2 = a little bit, 3 = somewhat, 4 = quite a bit, 5 = very much) or frequency ("never" to "always"). Raw scores are converted based on consistent metric (T-distribution) with data from the US general population with a T-score mean of 50 and standard deviation of 10.	Baseline and 6 Months
Secondary	6 Month Change in Quality of Life Evaluated by the Parkinson Disease Questionnaire 39 (PDQ-39)	The PDQ-39 is a 39-item self-report questionnaire, which assesses Parkinson's disease-specific health related quality over the last month covering 8 dimensions 1) Mobility (10, #1-10) 2) Activities of daily living (ADL) (6, #11-16) 3) Emotional well-being (6, #17-22) 4) Stigma (4, #23-26) 5) Social support (3, #27-29) 6) Cognition (4, #30-33) 7) Communication (3, #34-36) 8) Bodily discomfort (3, #37-39) on a 5 point ordinal system (0=never, 4=always). Dimension score = sum of scores of each item in the dimension divided by the maximum possible score of all the items in the dimension, multiplied by 100. Each dimension total score range from 0 (never have difficulty) to 100 (always have difficulty). Lower scores reflect better QoL. Overall score can be summarized in the Parkinson's Disease Summary Index (PDSI) or PDQ-39 Summary Index (PDQ-39 SI).PDSI or PDQ-39 SI = sum of dimension total scores divided by 8.	Baseline and 6 Months
Secondary	The Boston Naming Test	The examiner begins with Item 1 and continues through Item 60, unless the patient is in distress or refuses to continue. The patient is told to tell the examiner the name of each picture and is given about 20 seconds to respond for each trial. The examiner writes down the patient's responses in detail, using codes. If the patient fails to give the correct response, the examiner at her or his discretion may give the patient a phonemic cue, which is the initial sound of the target word. After the patient completes the test, the examiner scores each item + or - according to the response coding and scoring procedures.	Baseline and 6 Months
Secondary	Verbal Fluency Test	The Verbal Fluency Test has two conditions, Letter Verbal Fluency and Category Verbal Fluency. Letter Verbal Fluency assesses the number of words beginning with certain letters that participants can generate within 60 seconds, the Category Verbal Fluency assesses the number of words within particular categories participants can generate within 60 seconds.	Baseline and 6 Months
Secondary	Benton Judgement of Line Orientation Test	Benton Judgment of Line Orientation Test is a standardized test with 30 items that is specific for visual spatial cognition. Tests will be administered at baseline, after 3, 6, 9 and 12 months of treatment.; The minimum score is 0, indicating low visual spatial cognition. The maximum score is 30, indicating high visual spatial cognition	Baseline and 6 Months
Secondary	Intersecting Pentagon Copying Test	This involves the participant copying an intersecting double pentagon and is given a maximum score of 1 point based on the correctness of copying. The IPC addresses visuospatial constructional skills and executive function.	Baseline and 6 Months
Secondary	Mini Balance Evaluation Systems Test	Measure of dynamic balance, scores range from 0 (no Balance) to 28 good dynamic balance	Baseline and 6 Months
Secondary	Timed Up and Go Test (TUG)	This measures the time (in seconds) taken by a patient to rise to their feet from a sitting position, walk 3 metres in a straight line, turn around, walk back to the seat and sit down again	Baseline and 6 Months
Secondary	Six Minute Walk Test	Distance traveled during 6 minute walk	Baseline and 6 Months
Secondary	Activities Specific Balance Confidence Scale	The activities specific balance confidence scale is used to assess the level of fear of falling. It consists of 16 items reflecting the level of balance confidence from 0% (no confidence) to 100% (complete confidence)	Baseline and 6 Months
Secondary	New Freezing of Gait Questionnaire	The New Freezing of Gait Questionnaire (NFOG-Q) is a clinician-administered tool that aims to assess both the clinical aspects of FOG as well as its subsequent impairments on quality of life. The task ratings and scales are calculated into a summed NFOG-Q score. Part I detected the presence of FOG using a dichotomous item in which individuals were classified as a freezer (FR) or a non-freezer (NFR) if they had experienced FOG-episodes during the past month. Parts II and III were designed for FRs only, providing a total summed score between 0 and 28. Part II (items 2-6, scoring range 0-19) rated the severity of FOG based on its duration and frequency in its most common manifestation, i.e. during turning and initiation of gait. Part III rated the impact of FOG on daily life (items 7-9, scoring range 0-9). No separate on and off rating of parts II and III was considered to avoid unreliable assessment.	Baseline and 6 Months
Secondary	6 Month Change in Hippocampus Volumes on Structural MRI	Change in hippocampus volumes on structural MRI	Baseline and 6 Months
Secondary	6 Month Change in Microstructural Integrity of White Matter Pathways on Diffusion Tensor Imaging	Change in Microstructural integrity of white matter pathways on diffusion tensor imaging	Baseline and 6 Months
Secondary	6 Month Change in Functional Connectivity Among Brain Networks on Resting State fMRI	Change in Functional connectivity among brain networks on resting state fMRI	Baseline and 6 Months
Secondary	6 Month Change in Salivary Cortisol Levels	Change in salivary cortisol levels between baseline and 6 months post exercise. Cortisol samples were taken before the exercise intervention (Pre) and after the exercise intervention (Post) at 8 different time points: At awakening (0), 15 minutes post awakening (0.25), 30 minutes post awakening (0.5), 45 minutes post awakening (0.75), 3 hours post awakening (3), 6 hours post awakening (6), 9 hours post awakening (9), and 12 hours post awakening (12).	Baseline and 6 Months
Secondary	6 Month Change in Soluble Inflammatory Biomarkers in Plasma	Change in soluble inflammatory biomarkers in plasma between baseline and 6 months post exercise	Baseline and 6 Months
Secondary	6 Month Change in Peripheral Levels of Neurotrophic Factors in Plasma	Change in peripheral levels of neurotrophic factors in plasma between baseline and 6 months post exercise	Baseline and 6 Months