CClinicalTrials.gg
Not yet recruitingNCT07613112Updated Sep 29, 2026

Longitudinal Natural History Protocol for PRKN- and PINK1-Linked PD

An observational study in PARKINSON DIS, sponsored by National Institute of Neurological Disorders and Stroke (NINDS). Not yet recruiting at 1 site in United States. Open to participants aged 18 Years to 100 Years. Per ClinicalTrials.gov, last updated 2026-09-29.

Sponsored by National Institute of Neurological Disorders and Stroke (NINDS) · Observational

Study type
Observational
Model
Cohort
Time perspective
Prospective
Enrollment
70
Ages
18 Years to 100 Years
Sex
All
01

Study summary

Background:

Parkinson s disease is a neurologic disorder that affects movement. Its cause is unknown, and it usually begins later in life. Gene changes (PRKN and PINK1) can also cause rare types of Parkinson s disease that start at a young age. Researchers want to conduct a natural history study to learn more about how genes play a role in Parkinson s disease.

Objective:

To collect data and biological samples from people with different types of Parkinson s disease.

Eligibility:

People aged 18 to 80 years with either Parkinson s disease or PRKN- and PINK1-linked Parkinson s disease. Healthy volunteers are also needed.

Design:

Participants will have 6 clinic visits over 5 years. Each visit may take 1 to 3 days.

During each visit:

Participants will have a physical exam. The exam will be videotaped.

They will answer questions about their movement, thinking, mood, and sense of smell. The extent of any symptoms of Parkinson s disease will be evaluated: Participants movements may be assessed with a finger tapping test. They may be asked to scratch and sniff different scented strips to identify odors.

They will wear motion sensors on their arms, legs, chest, and back at the clinic. They will wear motion sensor devices on their wrists at home for 1 week.

Blood and urine samples will be collected.

Other tests are optional:

Magnetic resonance imaging (MRI) scan of the brain. Participants will lie on a table that slides into a tube.

Lumbar puncture (spinal tap). A thin needle will be inserted into their lower back to draw out a sample of the fluid around their spinal cord.

Muscle biopsy. A small sample of tissue will be taken from the leg.

Read the detailed description

Study Description:

This is a longitudinal, observational study that aims to assess progression of clinical features, imaging, and biologic markers of PD in study participants with and without manifest PD who are bi-allelic or mono-allelic carriers of pathogenic variants in the recessively inherited genes PRKN and PINK1 that represent prototypes of mitochondrial- associated PD.

Objectives:

Primary Objective: To characterize the natural history of motor symptoms in PRKN- and PINK1-linked PD.

Secondary Objectives: To comprehensively characterize other clinical features of PRKN- and PINK1-linked PD over time

Tertiary Objectives:

  • To characterize structural brain changes over time
  • To identify molecular signatures that differ between PRKN and PINK1-associated PD, non-manifesting mutation carriers, wildtype PD, and healthy controls.
  • To generate a repository of longitudinal data and samples for future studies aimed at developing targeted therapies.
  • To characterize in-home assessment of movements
  • To evaluate for mitochondrial changes in the muscle

Endpoints:

Primary Endpoint: Annual change in MDS Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III

Secondary Endpoints:

  • Annual change in MDS-UPDRS parts I, II, IV
  • Annual change in Montreal Cognitive Assessment (MoCA)
  • Annual change in Timed up and go (TUG)
  • Annual change in 10-meter walk
  • Annual change in 360 degree turn
  • Annual change in Unified Dyskinesia Rating Scale (UDysRS)
  • Annual change in University of Pennsylvania Smell Identification Test (UPSIT)
  • Annual change in REM-Sleep-Behavior Disorder Screening Questionnaire (RBD-SQ)
  • Annual change in Questionnaire for Impulsive-Compulsive Disorders (QUIP)
  • Annual change in Epworth Sleepiness Scale (ESS)
  • Annual change in Geriatric Depression Scale (GDS)
  • Annual change in State-Trait Anxiety Inventory (STAI)
  • Annual change in Scales for Outcomes in Parkinson s Disease - Autonomic Dysfunction (SCOPA AUT)
  • Annual change in 39-item Parkinson s Disease Questionnaire (PDQ-39)- quality of life measurement
  • Annual change in Schwab and England Activities of Daily Living (SE-ADL) scale
  • Annual change in Hoehn and Yahr scale assessment Tertiary endpoints:
  • Annual change of brain MRI measurement of overall brain, striatum and substantia nigra volumes
  • Annual change of brain MRI measurement of iron deposition
  • Annual change in studies from blood
  • Annual change in studies from CSF
  • Annual change in studies from urine
  • Annual change in Wearable Accelerometry data
  • Evidence of mitochondrial cytopathy on muscle biopsy
02

Conditions studied

  • PARKINSON DIS

Keywords

  • PINK1
  • PRKN
  • PARKINSON
03

Who can participate

Ages eligible
18 Years to 100 Years
Sexes eligible
All
Accepts healthy volunteers
No
Sampling method
Non-probability sample

Study population

There will be a total of up to 50 male or female participants 18- 80 years of age and older in 5 cohorts. Target number of completers for each cohort are listed below: - PD mito-biallelic (PD participants carrying two pathogenic variants in PRKN or PINK1): up to 15 - PD mito-monoallelic (PD participants carrying one pathogenic mono-allelic variant in PRKN and/or PINK1): up to 10 - PD idiopathic: up to 5 - Non-manifesting mito (participants who carry one or two pathogenic variants in PRKN and/or PINK1 but do not have a diagnosis of PD): up to 15 - Healthy controls: up to 5

Inclusion criteria

To be eligible to participate in this study, an individual must meet all of the following criteria:

All participants:

  • Stated willingness to comply with all study procedures and availability for the duration of the study
  • Male or female between the ages of 18-80 years old
  • Ability of subject to understand and the willingness to sign an informed consent document
  • Ability of subject to travel to the NIH Clinical Center

Additional inclusion criteria for each cohort as below:

PD Mito - Biallelic:

  • Established clinical diagnosis of Parkinson's disease
  • Two Pathogenic or likely pathogenic variants in PRKN or PINK1

PD Mito - Monoallelic:

  • Established clinical diagnosis of Parkinson's disease
  • One Pathogenic or likely pathogenic variant in PRKN and/or PINK1

Idiopathic Parkinson's Disease (PD):

  • Established clinical diagnosis of Parkinson's disease
  • Etiology of PD is idiopathic/sporadic based on investigator determination

Non-manifesting mito:

  • One or two pathogenic or likely pathogenic variant in PRKN and/or PINK1
  • Lack of clinical diagnosis of Parkinson's disease
  • Lack of current or clinically significant neurological disorder (based on investigator determination)

Healthy Volunteer

-Lack of current or clinically significant neurological disorder (based on investigator determination)

Exclusion criteria

EXCLUSION CRITERIA:

An individual who meets any of the following criteria will be excluded from participation in this study:

All participants:

  • Symptomatic PD syndromes due to drugs (e.g., metoclopramide, flunarizine, neuroleptics), metabolic disorders (e.g., Wilson's disease hypothyroidism), encephalitis, brain lesion, atypical parkinsonism, other monogenic forms of PD (e.g., GBA1, LRRK2, SNCA, VPS35, CHCHD2, DJ1, ATP13A2) other genetic disorders that may cause parkinsonism (e.g., spinocerebellar ataxia, X-linked dystonia parkinsonism)
  • Pregnancy at time of study enrollment
  • Any other reason that, in the opinion of the investigator, would render the participant unsuitable for study enrollment
  • Unwilling to allow samples or data to be shared with other researchers or institutions.
  • NIH staff or family members of study team members

Healthy Volunteer:

-Participants who become pregnant during the study will be withdrawn from further study procedures at the time pregnancy is identified.

Procedural Exclusions:

Subjects may still be enrolled if they cannot participate in certain procedures due to not meeting the inclusion requirements for that specific procedure. Subjects who meet exclusion criteria for procedures listed below may still undergo the procedure at a later time if the reason of exclusion is no longer present.

Brain MRI:

  • Contraindications to MRI such as a contraindicated non-removable metal device (i.e., pacemaker, defibrillator, insulin pump, metal clips, non-removable jewelry)
  • Pregnancy

Accelerometer:

-Non ambulatory

Lumbar puncture procedure:

  • PT/PTT values that are prolonged greater than or equal to 3 seconds from the upper limit of normal (including treatment with oral and parenteral anticoagulants)
  • INR greater than 1.4, thrombocytopenia (\<70,000), or abnormal bleeding time or platelet dysfunction
  • History of a bleeding disorder
  • Use of anticoagulants or antiplatelets
  • Pregnancy
  • History of headache requiring blood patch after a previous LP

Needle muscle biopsy:

  • PT/PTT values that are prolonged greater than or equal to 3 seconds from the upper limit of normal (including treatment with oral and parenteral anticoagulants)
  • INR greater than 1.4, thrombocytopenia (\<70,000), or abnormal bleeding time or platelet dysfunction
  • History of a bleeding disorder
  • Use of anticoagulants or antiplatelets
  • Pregnancy
04

Study design

Observational model
Cohort
Time perspective
Prospective
Enrollment
70 participants (estimated)

Groups and cohorts

  • Healthy controls

    Lack of current or clinically significant neurological disorder (based on investigator determination).

  • Non-manifesting mito

    participants who carry one or two pathogenic variants in PRKN and/or PINK1 but do not have a diagnosis of PD

  • PD idiopathic

    PD participants with idiopathic PD

  • PD mito - monoallelic

    Monoallelic: PD participants carrying one pathogenic mono-allelic variant in PRKN and/or PINK1

  • PD mito - biallelic

    Biallelic: PD participants carrying two pathogenic variants in PRKN or PINK1

05

What researchers measure

Primary outcomes

  1. Estimation of progression of motor symptoms across cohorts

    Measured by annual change in MDS Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III

    Time frame: When final patient completes their last visit

Secondary outcomes

  1. Annual change in MDS-UPDRS parts I, II, IV

    Characterization of other clinical features of PRKN- and PINK1- linked PD over time

    Time frame: When final patient completes their last visit

  2. Annual change in Montreal Cognitive Assessment (MoCA)

    Characterization of other clinical features of PRKN- and PINK1- linked PD over time

    Time frame: When final patient completes their last visit

  3. Annual change in Timed up and go (TUG)

    Characterization of other clinical features of PRKN- and PINK1- linked PD over time

    Time frame: When final patient completes their last visit

  4. Annual change in 10-meter walk

    Characterization of other clinical features of PRKN- and PINK1- linked PD over time

    Time frame: When final patient completes their last visit

  5. Annual change in 360 degree turn

    Characterization of other clinical features of PRKN- and PINK1- linked PD over time

    Time frame: When final patient completes their last visit

  6. Annual change in Unified Dyskinesia Rating Scale (UDysRS)

    Characterization of other clinical features of PRKN- and PINK1- linked PD over time

    Time frame: When final patient completes their last visit

  7. Annual change in University of Pennsylvania Smell Identification Test (UPSIT)

    Characterization of other clinical features of PRKN- and PINK1- linked PD over time

    Time frame: When final patient completes their last visit

  8. Annual change in REM-Sleep-Behavior Disorder Screening Questionnaire (RBD-SQ)

    Characterization of other clinical features of PRKN- and PINK1- linked PD over time

    Time frame: When final patient completes their last visit

  9. Annual change in Questionnaire for Impulsive-Compulsive Disorders (QUIP)

    Characterization of other clinical features of PRKN- and PINK1- linked PD over time

    Time frame: When final patient completes their last visit

  10. Annual change in Epworth Sleepiness Scale (ESS)

    Characterization of other clinical features of PRKN- and PINK1- linked PD over time

    Time frame: When final patient completes their last visit

  11. Annual change in Geriatric Depression Scale (GDS)

    Characterization of other clinical features of PRKN- and PINK1- linked PD over time

    Time frame: When final patient completes their last visit

  12. Annual change in State-Trait Anxiety Inventory (STAI)

    Characterization of other clinical features of PRKN- and PINK1- linked PD over time

    Time frame: When final patient completes their last visit

  13. Annual change in Scales for Outcomes in Parkinson's Disease - Autonomic Dysfunction (SCOPA AUT)

    Characterization of other clinical features of PRKN- and PINK1- linked PD over time

    Time frame: When final patient completes their last visit

  14. Annual change in 39-item Parkinson's Disease Questionnaire (PDQ-39) - quality of life measurement

    Characterization of other clinical features of PRKN- and PINK1- linked PD over time

    Time frame: When final patient completes their last visit

  15. Annual change in Schwab and England Activities of Daily Living (SE-ADL) scale

    Characterization of other clinical features of PRKN- and PINK1- linked PD over time

    Time frame: When final patient completes their last visit

  16. Annual change in Hoehn and Yahr scale assessment

    Characterization of other clinical features of PRKN- and PINK1- linked PD over time

    Time frame: When final patient completes their last visit

06

Study locations

1 site
  • National Institutes of Health Clinical Center
    Bethesda, Maryland 20892, United States
    • NIH Clinical Center Office of Patient Recruitment (OPR) · Contact · ccopr@nih.gov · 800-411-1222
07

References and documents

Individual participant data

Plan to share: Undecided

08

Registry details

Key details

Study ID
NCT07613112
Lead sponsor
National Institute of Neurological Disorders and Stroke (NINDS)
Responsible party
Sponsor
First posted
May 29, 2026
Start date
Oct 4, 2026 (estimated)
Primary completion
May 30, 2036 (estimated)
Completion
May 30, 2036 (estimated)
Last update
Sep 29, 2026

Study contacts

Oday K Halhouli, M.D.
Contact
oday.halhouli@nih.gov
(301) 402-7969
Debra J Ehrlich, M.D.
Contact
debra.ehrlich@nih.gov
(301) 443-7888
Debra J Ehrlich, M.D.
principal investigator · National Institute of Neurological Disorders and Stroke (NINDS)

Oversight

FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is not yet recruiting, as verified in Sep 2026. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Start the discussion