Progressive Supranuclear PalsyPhase 2NCT00005903
Continuously Infused Recombinant-Methionyl Human Glial Cell Line-Derived Neurotrophic Factor (GDNF) to Treat Progressive Supranuclear Palsy
A Phase 2 study testing GDNF & Synchro Med Infusion System in people with Progressive Supranuclear Palsy, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
Trial summary
This study will examine the safety and effectiveness of an experimental drug called GDNF delivered through an investigational device to treat progressive supranuclear palsy (PSP). The drug will be administered directly into the brain through catheters attached to an infusion pump implanted in the abdomen. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Progressive Supranuclear Palsy
- What is being tested?
- GDNF & Synchro Med Infusion System
- Type of treatment
- Injection or infusion
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2000to May 2005
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Diagnosis of PSP with bilateral symptoms based on medical history and neurologic examination in accordance with NINDS criteria. Those evidencing ratable limb dysfunction bilaterally as well as a past history levodopa responsivity will be especially sought.
- PSP will be considered clinically to be at a moderate to moderately advanced stage (PSP Staging System grade BB - DD), associated with ratable parkinsonian signs in the limbs bilaterally and a Hoehn and Yahr grade of 3 - 5.
- Men or nonpregnant women age 35 to 75 years. Women of childbearing potential must have a negative human chorionic gonadotropin (HCG) test result immediately before (within 48 hours) catheter and pump implantation and repeated again immediately before (within 48 hours) the start of drug infusion; men and women of childbearing potential must practice adequate contraception during the course of the study.
- Before any study-specific procedures are performed, the subject and their designated representative must give signed informed consent for their participation. All patients must sign a Durable Power of Attorney (DPA). Device implantation must occur within 60 days after a subject consents to participate in the study.
- The subject is medically able to undergo the surgical procedures required to implant bilateral pumps and intracranial catheters using stereotactic procedures.
Who cannot join
- Treatment with levodopa, dopamine agonists or any other antiparkinsonian medications.
- Presence of clinically significant psychosis or hallucinations.
- Any disorder that precludes a surgical procedure (e.g., bleeding diathesis, signs of sepsis or inadequately treated infection) alters wound healing or renders bilateral catheter and infusion pump implants unsuitable.
- Any history of clinically significant head trauma or cerebrovascular disease or recent history (within previous 2 years) of drug or alcohol abuse.
- A computed tomography (CT) scan or magnetic resonance image (MRI) of the brain within 3 months before the implantation procedure that indicates the presence of a central nervous system abnormality that may interfere with the assessments of safety or biologic effect in this protocol, or represent a surgical risk to the subject.
- The presence of an intracranial shunt or catheter system other than the one used in this protocol.
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- Any medical disability, condition or laboratory abnormality (e.g., severe degenerative arthritis, compromised nutritional state, body weight less than 15% of ideal, Na less than 130 (grade 3 or above), cardiovascular disease) that would be deemed likely to increase risk of participation in the protocol or interfere with assessment of the safety and biologic effect of study materials, the chronic implantation of catheters and infusion pumps, or would compromise the ability of the subject to give informed consent.
- Known allergy to E coli-derived products or history of anaphylaxis.
- Treatment with an investigational agent or used an investigational device within 60 days before the first dose of study material, other than those described in this protocol.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institute of Neurological Disorders and Stroke (NINDS)
Bethesda, Maryland, 20892
About this study
Official title: Dose-Escalation Trial of Continuously Infused Recombinant-Methionyl Human Glial Cell Line-Derived Neurotrophic Factor for the Treatment of PSP
This study will examine the safety and effectiveness of an experimental drug called GDNF delivered through an investigational device to treat progressive supranuclear palsy (PSP). The drug will be administered directly into the brain through catheters attached to an infusion pump implanted in the abdomen. The study will evaluate 1) if the drug is safe and well tolerated when given by this method; 2) the performance of the catheters and pump system, and 3) the effects of GDNF on PSP symptoms.
PSP is a rare neurological disease that causes eye movement dysfunction, muscle rigidity, slowness of movement, swallowing, speech, emotional, cognitive and personality problems. Patients 35 to 75 years old with PSP may be eligible for this study. Candidates will be screened at the National Institutes of Health outpatient clinic in Bethesda, MD, with a medical history, physical examination, neurological and neuropsychiatric evaluations, blood tests, electrocardiogram, CT scan of the brain, and baseline studies including a special eye examination, evaluation of symptoms, lumbar puncture (spinal tap) and psychiatric interview.
Read more
Patients enrolled in the study will undergo surgery to place two catheters into the brain and two infusion pumps under the skin in the upper abdomen. The surgery will be performed at Vanderbilt University Medical Center in Nashville, TN. It will be done under general anesthesia and will require a 3 day hospitalization. Within 24 hours after the surgery, a CT scan of the brain will be done to ensure the catheters are properly placed. Patients return to NIH two weeks after surgery for post-surgery examination and treatment initiation.
All patients will receive continuous infusions of GNDF through one catheter and placebo (an inactive salt solution) through the other for 6 months. Half of the patients will receive placebo in the right side of the brain and GNDF in the left, and half will receive GNDF in the right side of the brain and placebo in the left. All patients will also undergo the following procedures:
Brief physical examination, and evaluation of symptoms and adverse side effects - every 2 weeks
Blood and urine tests - every 2 weeks for the first 2 months and then every 8 weeks until the end of the study
CT scan to check catheter placement - weeks 9 and 27
Thorough evaluation of symptoms - before beginning treatment and weeks 1, 5, 9, 17 and 27
Neuropsychiatric evaluation - week 27
Special eye examination - weeks 1 and 27
Lumbar puncture - week 27
Additional blood tests to measure drug concentration and antibodies - 6 times during the study
In addition, some patients may be asked to have positron emission tomography (PET) scans or a single photon emission tomography (SPECT) scan, or both.
The potential benefit of GDNF is unknown. In studies with rats and monkeys, GNDF increased the number and size of brain cells containing the chemical messenger dopamine and some movement and balance problems were lessened. Earlier studies of GDNF infused into the ventricles of patients with Parkinson's disease showed no benefit and no serious harm.
Read the detailed description
The safety and initial efficacy of the unilateral intralenticular infusion of recombinant-methionyl human glial cell line-derived neurotrophic factor (r-metHuGDNF) will be compared with the contralateral intralenticular infusion of a placebo solution, both continuously administered using chronically implanted catheters and pumps in up to 10 patients with progressive supranuclear palsy. Safety will be evaluated by analyzing implant-, post-implant-, and treatment-emergent adverse events, clinical laboratory test results, and disease status. Efficacy will be studied by comparing left and right sided neurologic function using validated clinical scales as well as by putative surrogate biochemical and radiographic measures.
- Conditions
- Progressive Supranuclear Palsy
- Being tested
- GDNF & Synchro Med Infusion System
- Keywords
- Parkinsonism, Trophic Factor, Neurodegenerative Disorder, Progressive Supranuclear Palsy
- Medical subject headings
- Supranuclear Palsy, Progressive, Parkinsonian Disorders, Neurodegenerative Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GDNF & Synchro Med Infusion SystemDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jun 2000 (estimated)
- Study startJun 2000
- Study completionMay 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Progressive Supranuclear PalsyStudies of the same condition, open and under way.
- More trials run by National Institute of Neurological Disorders and Stroke (NINDS)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Enrolment
- 15 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00005903
- Sponsor's protocol ID
- 000145
- Other IDs
- 00-N-0145
- Status last verified
- May 2005
- First submitted
- 7 Jun 2000
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
Litvan I. The clinical and pathologic hallmarks of progressive supranuclear palsy. Curr Opin Neurol. 1997 Aug;10(4):346-50. doi: 10.1097/00019052-199708000-00011.
PubMed 9266160Santacruz P, Uttl B, Litvan I, Grafman J. Progressive supranuclear palsy: a survey of the disease course. Neurology. 1998 Jun;50(6):1637-47. doi: 10.1212/wnl.50.6.1637.
PubMed 9633705Pahwa R. Progressive supranuclear palsy. Med Clin North Am. 1999 Mar;83(2):369-79, v-vi. doi: 10.1016/s0025-7125(05)70109-7.
PubMed 10093583
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dose-Escalation Trial of Continuously Infused Recombinant-Methionyl Human Glial Cell Line-Derived Neurotrophic Factor for the Treatment of PSP
- ClinicalTrials.gov ID
- NCT00005903
- Acronym / sponsor ID
- 000145
- Conditions
- Progressive Supranuclear Palsy
- Keywords
- Parkinsonism, Trophic Factor, Neurodegenerative Disorder, Progressive Supranuclear Palsy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- Jun 2000
- Study completion
- May 2005
- First posted
- 8 Jun 2000 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will examine the safety and effectiveness of an experimental drug called GDNF delivered through an investigational device to treat progressive supranuclear palsy (PSP). The drug will be administered directly into the brain through catheters attached to an infusion pump implanted in the abdomen. The study will evaluate 1) if the drug is safe and well tolerated when given by this method; 2) the performance of the catheters and pump system, and 3) the effects of GDNF on PSP symptoms.
PSP is a rare neurological disease that causes eye movement dysfunction, muscle rigidity, slowness of movement, swallowing, speech, emotional, cognitive and personality problems. Patients 35 to 75 years old with PSP may be eligible for this study. Candidates will be screened at the National Institutes of Health outpatient clinic in Bethesda, MD, with a medical history, physical examination, neurological and neuropsychiatric evaluations, blood tests, electrocardiogram, CT scan of the brain, and baseline studies including a special eye examination, evaluation of symptoms, lumbar puncture (spinal tap) and psychiatric interview.
Patients enrolled in the study will undergo surgery to place two catheters into the brain and two infusion pumps under the skin in the upper abdomen. The surgery will be performed at Vanderbilt University Medical Center in Nashville, TN. It will be done under general anesthesia and will require a 3 day hospitalization. Within 24 hours after the surgery, a CT scan of the brain will be done to ensure the catheters are properly placed. Patients return to NIH two weeks after surgery for post-surgery examination and treatment initiation.
All patients will receive continuous infusions of GNDF through one catheter and placebo (an inactive salt solution) through the other for 6 months. Half of the patients will receive placebo in the right side of the brain and GNDF in the left, and half will receive GNDF in the right side of the brain and placebo in the left. All patients will also undergo the following procedures:
Brief physical examination, and evaluation of symptoms and adverse side effects - every 2 weeks
Blood and urine tests - every 2 weeks for the first 2 months and then every 8 weeks until the end of the study
CT scan to check catheter placement - weeks 9 and 27
Thorough evaluation of symptoms - before beginning treatment and weeks 1, 5, 9, 17 and 27
Neuropsychiatric evaluation - week 27
Special eye examination - weeks 1 and 27
Lumbar puncture - week 27
Additional blood tests to measure drug concentration and antibodies - 6 times during the study
In addition, some patients may be asked to have positron emission tomography (PET) scans or a single photon emission tomography (SPECT) scan, or both.
The potential benefit of GDNF is unknown. In studies with rats and monkeys, GNDF increased the number and size of brain cells containing the chemical messenger dopamine and some movement and balance problems were lessened. Earlier studies of GDNF infused into the ventricles of patients with Parkinson's disease showed no benefit and no serious harm.
Detailed description
The safety and initial efficacy of the unilateral intralenticular infusion of recombinant-methionyl human glial cell line-derived neurotrophic factor (r-metHuGDNF) will be compared with the contralateral intralenticular infusion of a placebo solution, both continuously administered using chronically implanted catheters and pumps in up to 10 patients with progressive supranuclear palsy. Safety will be evaluated by analyzing implant-, post-implant-, and treatment-emergent adverse events, clinical laboratory test results, and disease status. Efficacy will be studied by comparing left and right sided neurologic function using validated clinical scales as well as by putative surrogate biochemical and radiographic measures.
Study design
- Primary purpose
- Treatment
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- Diagnosis of PSP with bilateral symptoms based on medical history and neurologic examination in accordance with NINDS criteria. Those evidencing ratable limb dysfunction bilaterally as well as a past history levodopa responsivity will be especially sought.
- PSP will be considered clinically to be at a moderate to moderately advanced stage (PSP Staging System grade BB - DD), associated with ratable parkinsonian signs in the limbs bilaterally and a Hoehn and Yahr grade of 3 - 5.
- Men or nonpregnant women age 35 to 75 years. Women of childbearing potential must have a negative human chorionic gonadotropin (HCG) test result immediately before (within 48 hours) catheter and pump implantation and repeated again immediately before (within 48 hours) the start of drug infusion; men and women of childbearing potential must practice adequate contraception during the course of the study.
- Before any study-specific procedures are performed, the subject and their designated representative must give signed informed consent for their participation. All patients must sign a Durable Power of Attorney (DPA). Device implantation must occur within 60 days after a subject consents to participate in the study.
- The subject is medically able to undergo the surgical procedures required to implant bilateral pumps and intracranial catheters using stereotactic procedures.
Key exclusion criteria (9 listed)
- Treatment with levodopa, dopamine agonists or any other antiparkinsonian medications.
- Presence of clinically significant psychosis or hallucinations.
- Any disorder that precludes a surgical procedure (e.g., bleeding diathesis, signs of sepsis or inadequately treated infection) alters wound healing or renders bilateral catheter and infusion pump implants unsuitable.
- Any history of clinically significant head trauma or cerebrovascular disease or recent history (within previous 2 years) of drug or alcohol abuse.
- A computed tomography (CT) scan or magnetic resonance image (MRI) of the brain within 3 months before the implantation procedure that indicates the presence of a central nervous system abnormality that may interfere with the assessments of safety or biologic effect in this protocol, or represent a surgical risk to the subject.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GDNF & Synchro Med Infusion System | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2008.
- Background: PubMed 9266160Litvan I. The clinical and pathologic hallmarks of progressive supranuclear palsy. Curr Opin Neurol. 1997 Aug;10(4):346-50. doi: 10.1097/00019052-199708000-00011.
- Background: PubMed 9633705Santacruz P, Uttl B, Litvan I, Grafman J. Progressive supranuclear palsy: a survey of the disease course. Neurology. 1998 Jun;50(6):1637-47. doi: 10.1212/wnl.50.6.1637.
- Background: PubMed 10093583Pahwa R. Progressive supranuclear palsy. Med Clin North Am. 1999 Mar;83(2):369-79, v-vi. doi: 10.1016/s0025-7125(05)70109-7.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing GDNF & Synchro Med Infusion System in people with Progressive Supranuclear Palsy, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Mar 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00005903, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2008.