A Phase 2 interventional study of TISSEEL in Cerebrospinal Fluid Leaks, sponsored by Duke University. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-06-18.
Sponsored by Duke University · Phase 2, Interventional, and Treatment
Among 12 studies in Cerebrospinal Fluid Leak with a site in United States — 2 open to participants now, 2 under way, none of them phase 3. Cerebrospinal Fluid Leak · United States.
Among the 12 studies in Cerebrospinal Fluid Leak with a site in United States, this one is the only one that started in 2017, is one of 2 in phase 2, and was the 5th registered.
41 studies on the registry are indexed under Cerebrospinal Fluid Leak; 9 are open to participants now.
Browse Cerebrospinal Fluid Leak studies →2 of the 12 studies in Cerebrospinal Fluid Leak with a site in United States are open now. Recruiting first, the newest first:
Pramand LLC · Sites in United States
Ages 18+
Indiana University · Sites in United States
Ages 18+ · Healthy volunteers
A study can be open while its sites in United States have not opened yet or have stopped. Only those recruiting at a site in United States →
Of the 7 Cerebrospinal Fluid Leak studies recruiting now, 5 set no upper age limit and 1 stops at 75 or younger; 1 takes children under 18; 2 take healthy volunteers.
This study: 18 Years and older · all sexes · no healthy volunteers.
The full table on the hub →This tab as a report to print or save as PDF → With an account.
12 studies; the count open now beside each. This study's row is marked.
First in 2011; this study’s year is marked. 1 started in 2017.
By drug class, each counting the studies that test any of its medicines:
This study's enrollment of 15 is below the median of 74 across 24 interventional studies indexed under Cerebrospinal Fluid Leak.
Median enrollment 146 across the 8 interventional studies, 215 across the 4 observational. Of the 9 that completed or were terminated, 4 (44%) have results posted.
This tab as a report to print or save as PDF → With an account.
7 of 12 have an industry lead sponsor. The 10 most frequent:
Duke University is the lead sponsor of 2,063 studies on the registry; 272 are open to participants now.
Of its 204 completed or terminated interventional studies of FDA-regulated products, 167 (82%) have results posted.
Duke University has 1 study filed under Cerebrospinal Fluid Leak — fewer than ten, so there is no comparison to draw.
2 of the studies in Cerebrospinal Fluid Leak with a site in United States that are under way reach primary completion within a year, 0 of them phase 3. Phase 3 first, then by date:
| Study | Primary completion |
|---|---|
| NCT05898074Indiana UniversityRole of Novel RADA16 Hydrogel in Endoscopic Skull Base Surgery | 2026-12-15 |
| NCT06406790Pramand LLCCraniSeal Post Approval Study | 2027-02 |
Add all 2 to your calendar (.ics) → With an account.
Among the 12 studies in Cerebrospinal Fluid Leak with a site in United States, from their registry updates:
Nothing recorded among them since 2026-09-25.
This tab as a report to print or save as PDF → With an account.
The goal of this randomized controlled trial (RCT) is to compare the efficacy of CT fluoroscopy-guided targeted epidural patching for treatment of imaging-confirmed spinal CSF leaks to that of a simulated procedure without patching material in patients with spontaneous intracranial hypotension.
Spontaneous intracranial hypotension (SIH) is a condition caused by non-iatrogenic spinal CSF leaks that classically presents with orthostatic headaches. These headaches, in conjunction with other presenting symptoms such as nausea, diplopia, tinnitus, and cognitive deficits, often result in profound disability. SIH is considerably underreported due to pervasive misdiagnosis. Thus, while the estimated annual incidence is reported to be 5 in 100,000, the actual number is likely considerably greater.
The current standard-of-care treatment for SIH cases that are refractory to conservative measures (i.e. bed rest and hydration) is percutaneous epidural blood patching (EBP) of the spinal CSF leak. Percutaneous EBP can be performed in several ways: 1) with or without imaging guidance, 2) targeted to a site of known or suspected CSF leak or non-targeted, and 3) with or without the addition of fibrin glue sealant.
The leading theory for the mechanism behind percutaneous EBP treatment of SIH is that it creates a durable seal of the CSF leak resulting in normalization of CSF hydrodynamics and a resultant diminution in symptoms. Fibrin glue, a sealant used for treatment of unintended durotomies during neurosurgery, is thought to improve the likelihood of a successful patch over patches containing blood alone. Therefore, imaging-guided targeted delivery of patching material containing both blood and fibrin glue directly to the site of CSF leak, a novel therapy, is presumed to be the optimal therapy. For this reason, this procedure has become standard-of-care at many tertiary-care institutions over the past several years.
Our group has extensive experience with CT fluoroscopy-guided targeted blood and fibrin glue patching of proven CSF leaks in SIH patients. However, significant uncertainty remains with regard to the efficacy of this procedure due to a paucity of outcomes data and the absence of any prospective RCTs. In fact, nearly all of the current evidence for the treatment of SIH is found in the form of retrospective chart reviews. Given the growing recognition of SIH, the fact that a known subset of patients will have spontaneous resolution of symptoms, and the absence of clear evidence to guide treatment, there is a critical need to evaluate the efficacy of targeted patching with blood and fibrin glue with a prospective RCT. Fulfilling this unmet need forms the basis for this proposal. While determining the efficacy of the other types of EBPs is also important, we aim to begin by evaluating the efficacy of the presumed optimal therapy.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CT fluoroscopy-guided blood and fibrin glue patching targeted to the site of CSF leak.
Drug: TISSEEL
Instead of injection of blood and fibrin glue patching material through the needles, an equivalent volume of preservative free sterile Elliots B solution will be injected.
Drug: TISSEEL
TISSEEL is a fibrin sealant indicated for use as an adjunct to hemostasis in adult and pediatric patients (\>1 month of age) undergoing surgery when control of bleeding by conventional surgical techniques (such as suture, ligature, and cautery) is ineffective or impractical. TISSEEL is effective in heparinized patients
Change in Median (Headache Impact Test-6) HIT-6 Score From Baseline
Absolute change in median HIT-6 score from pre-procedural baseline to 1 month post procedure for each group. The HIT-6 consists of six items: pain, social functioning, role functioning, vitality, cognitive functioning, and psychological distress. The patient answers each of the six related questions using one of the following five responses: "never", "rarely", "sometimes", "very often", or "always". These responses are summed to produce a total HIT-6 score that ranges from 36 to 78, where a higher score indicates a greater impact of headache on the daily life of the respondent.
Time frame: Baseline, 1 month
Change in Median HIT-6 Score From Baseline
Absolute change in median HIT-6 score from pre-procedural baseline to 2 weeks and 4 months post procedure for each group. The HIT-6 consists of six items: pain, social functioning, role functioning, vitality, cognitive functioning, and psychological distress. The patient answers each of the six related questions using one of the following five responses: "never", "rarely", "sometimes", "very often", or "always". These responses are summed to produce a total HIT-6 score that ranges from 36 to 78, where a higher score indicates a greater impact of headache on the daily life of the respondent.
Time frame: Baseline, 2 weeks, 4 months
Reduction in Median Migraine Disability Assessment (MIDAS) Score From Baseline
The MIDAS questionnaire assesses headache-related disability. Patients answer five questions, scoring the number of days, in the past 3 months, where their activity was limited due to headache. A higher score indicates greater headache-related disability. This tool has been shown to be internally consistent, highly reliable, valid, and correlates with physicians' clinical judgment. MIDAS Scale Range: 0 - 270
Time frame: Baseline, 2 weeks, 1 month, 4 months
Change in Median NRS Score From Baseline
The pain numerical rating scale (NRS) is a well-validated tool for quantitatively assessing patients' pain. The NRS asks patients to rate their current pain intensity on an 11-point scale ranging from 0 ("no pain") to 10 ("worst possible pain"). It has been found to be a valid measure of pain intensity with minimum clinically important difference noted to be a change of 2 points. The investigators will use NRS averaged over the past 24 hours for all time points in this trial. The Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) consensus statement indicates that an NRS reduction of 30% (or 2 points) is associated with a meaningful or moderately important improvement in pain. Further, IMMPACT also indicates that an NRS reduction of 50% (or 4 points) is associated with a substantial improvement in pain. The investigators will follow their consensus recommendations and explicitly report these two categories of pain relief.
Time frame: Baseline, 2 weeks, 1 month, 4 months
Change in Median EQ-5D (European Quality of Life-5 Dimensions) Score From Baseline
The EQ-5D is a standardized measure of health status that provides a simple, generic measure of health for clinical appraisal. It is well-validated for health status measurement and for quality-of-life in headache. Scores on the EQ-5D were calculated using the United States 3L, time trade off (TTO) valuation technique. Scores range from 0 to 1, with 1 indicating perfect health.
Time frame: Baseline, 2 weeks, 1 month, 4 months
Change in Median WPAI (Work Productivity and Activity Impairment) Score From Baseline
The WPAI is a validated instrument with good test-retest reliability used extensively in health research that quantifies impairment in daily activities and work productivity. Scores on the WPAI range from 0 - 100% with higher percentages indicating greater impact on work productivity and more severe activity impairment.
Time frame: Baseline, 2 weeks, 1 month, 4 months
Change in PGIC (Patient Global Impression of Change) Score From Baseline
PGIC is a validated 7-point Likert-type scale assessing a patient's overall impression of improvement after intervention. Scores range from 1 - 7 (1: no change or worsening of condition; 2: almost the same, hardly any change at all; 3: a little better, but no noticeable change; 4: somewhat better, but the change has not made any real difference; 5: moderately better, and a slight but noticeable change; 6: better and a definite improvement that has made a real and worthwhile difference; 7: a great deal better, and a considerable improvement that has made all the difference) with higher scores indicating greater improvement.
Time frame: Baseline, 2 weeks, 1 month, 4 months
| Milestone | Targeted Epidural Patching of CSF Leaks With Autologous Blood and Fibrin Glue | Simulated Patching Procedure |
|---|---|---|
| Started | 8 | 7 |
| Crossover at 2 months | 0 | 7 |
| Completed | 7 | 7 |
| Not completed | 1 | 0 |
| Withdrew: Withdrawal by subject | 1 | 0 |
Absolute change in median HIT-6 score from pre-procedural baseline to 1 month post procedure for each group. The HIT-6 consists of six items: pain, social functioning, role functioning, vitality, cognitive functioning, and psychological distress. The patient answers each of the six related questions using one of the following five responses: "never", "rarely", "sometimes", "very often", or "always". These responses are summed to produce a total HIT-6 score that ranges from 36 to 78, where a higher score indicates a greater impact of headache on the daily life of the respondent.
| score on a scale | Targeted Epidural Patching of CSF Leaks With Autologous Blood and Fibrin Glue | Simulated Patching Procedure |
|---|---|---|
| Change in Median (Headache Impact Test-6) HIT-6 Score From Baseline | -12 (-16 to -7) | -7 (-13 to -1) |
Absolute change in median HIT-6 score from pre-procedural baseline to 2 weeks and 4 months post procedure for each group. The HIT-6 consists of six items: pain, social functioning, role functioning, vitality, cognitive functioning, and psychological distress. The patient answers each of the six related questions using one of the following five responses: "never", "rarely", "sometimes", "very often", or "always". These responses are summed to produce a total HIT-6 score that ranges from 36 to 78, where a higher score indicates a greater impact of headache on the daily life of the respondent.
| units on a scale | Targeted Epidural Patching of CSF Leaks With Autologous Blood and Fibrin Glue | Simulated Patching Procedure |
|---|---|---|
| 2 weeks | -5.5 (-10 to 0.5) | -7 (-17 to -3) |
| 4 months | -4.5 (-16.5 to -1.5) | -12 (-24 to -7) |
The MIDAS questionnaire assesses headache-related disability. Patients answer five questions, scoring the number of days, in the past 3 months, where their activity was limited due to headache. A higher score indicates greater headache-related disability. This tool has been shown to be internally consistent, highly reliable, valid, and correlates with physicians' clinical judgment. MIDAS Scale Range: 0 - 270
| units on a scale | Targeted Epidural Patching of CSF Leaks With Autologous Blood and Fibrin Glue | Simulated Patching Procedure |
|---|---|---|
| 2 weeks | -25 (-55 to 6) | 16 (-35 to 100) |
| 1 month | -62.5 (-117 to -37) | -40 (-86 to -3) |
| 4 months | -87 (-134.5 to -69.5) | -53 (-210 to -22) |
The pain numerical rating scale (NRS) is a well-validated tool for quantitatively assessing patients' pain. The NRS asks patients to rate their current pain intensity on an 11-point scale ranging from 0 ("no pain") to 10 ("worst possible pain"). It has been found to be a valid measure of pain intensity with minimum clinically important difference noted to be a change of 2 points. The investigators will use NRS averaged over the past 24 hours for all time points in this trial. The Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) consensus statement indicates that an NRS reduction of 30% (or 2 points) is associated with a meaningful or moderately important improvement in pain. Further, IMMPACT also indicates that an NRS reduction of 50% (or 4 points) is associated with a substantial improvement in pain. The investigators will follow their consensus recommendations and explicitly report these two categories of pain relief.
| units on a scale | Targeted Epidural Patching of CSF Leaks With Autologous Blood and Fibrin Glue | Simulated Patching Procedure |
|---|---|---|
| 2 weeks | -0.5 (-1.5 to 1) | -1 (-3 to 0) |
| 1 month | -2.5 (-4.5 to -1) | 0 (-3 to 3) |
| 4 months | -1.5 (-5 to -0.5) | -2 (-3 to -1) |
The EQ-5D is a standardized measure of health status that provides a simple, generic measure of health for clinical appraisal. It is well-validated for health status measurement and for quality-of-life in headache. Scores on the EQ-5D were calculated using the United States 3L, time trade off (TTO) valuation technique. Scores range from 0 to 1, with 1 indicating perfect health.
| units on a scale | Targeted Epidural Patching of CSF Leaks With Autologous Blood and Fibrin Glue | Simulated Patching Procedure |
|---|---|---|
| 2 weeks | 0.1 (0 to 0.2) | 0.1 (-0.1 to 0.3) |
| 1 month | 0 (0 to 0.4) | 0.1 (0 to 0.4) |
| 4 months | 0 (-0.1 to 0.1) | 0.2 (0.1 to 0.4) |
The WPAI is a validated instrument with good test-retest reliability used extensively in health research that quantifies impairment in daily activities and work productivity. Scores on the WPAI range from 0 - 100% with higher percentages indicating greater impact on work productivity and more severe activity impairment.
| units on a scale | Targeted Epidural Patching of CSF Leaks With Autologous Blood and Fibrin Glue | Simulated Patching Procedure |
|---|---|---|
| 2 weeks | 1.3 (-16.9 to 13.5) | -0.3 (-8.8 to 3.6) |
| 1 month | -13.8 (-51 to 5) | -2.3 (-20.8 to 20) |
| 4 months | -9 (-29 to 13.7) | -28.5 (-47 to -10) |
PGIC is a validated 7-point Likert-type scale assessing a patient's overall impression of improvement after intervention. Scores range from 1 - 7 (1: no change or worsening of condition; 2: almost the same, hardly any change at all; 3: a little better, but no noticeable change; 4: somewhat better, but the change has not made any real difference; 5: moderately better, and a slight but noticeable change; 6: better and a definite improvement that has made a real and worthwhile difference; 7: a great deal better, and a considerable improvement that has made all the difference) with higher scores indicating greater improvement.
| score on a scale | Targeted Epidural Patching of CSF Leaks With Autologous Blood and Fibrin Glue | Simulated Patching Procedure |
|---|---|---|
| 2 weeks | 3.5 (3 to 4.5) | 2 (1 to 4) |
| 1 month | 4 (3 to 5.5) | 3 (1 to 5) |
| 4 months | 4.5 (3.5 to 6) | 6 (2 to 6) |
Collected over Adverse event data were collected immediately after the initial procedure, immediately after any crossover procedures (performed at the 2-month time point), and also at 1 week after any procedure (initial or crossover).. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Targeted Epidural Patching of CSF Leaks With Autologous Blood and Fibrin Glue | 0/15 (0%) | 0/15 (0%) | 1/15 (6.7%) |
| Simulated Patching Procedure | 0/7 (0%) | 0/7 (0%) | 1/7 (14.3%) |
| Event | Targeted Epidural Patching of CSF Leaks With Autologous Blood and Fibrin Glue | Simulated Patching Procedure |
|---|---|---|
| Asymptomatic self-limited hypertensionVascular disorders | 0/15 | 1/7 |
| Rebound Intracranial HypertensionNervous system disorders | 1/15 | 0/7 |
| Age, Categorical(Participants) | Targeted Epidural Patching of CSF Leaks With Autologous Blood and Fibrin Glue | Simulated Patching Procedure | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 7 | 5 | 12 |
| >=65 years | 1 | 2 | 3 |
| Age, Continuous(years) | Targeted Epidural Patching of CSF Leaks With Autologous Blood and Fibrin Glue | Simulated Patching Procedure | Total |
|---|---|---|---|
| Mean | 46.0 ± 13.1 | 57.6 ± 14.7 | 51.8 ± 13.9 |
| Sex: Female, Male(Participants) | Targeted Epidural Patching of CSF Leaks With Autologous Blood and Fibrin Glue | Simulated Patching Procedure | Total |
|---|---|---|---|
| Female | 7 | 5 | 12 |
| Male | 1 | 2 | 3 |
| Ethnicity (NIH/OMB)(Participants) | Targeted Epidural Patching of CSF Leaks With Autologous Blood and Fibrin Glue | Simulated Patching Procedure | Total |
|---|---|---|---|
| Hispanic or Latino | 0 | 0 | 0 |
| Not Hispanic or Latino | 7 | 7 | 14 |
| Unknown or Not Reported | 1 | 0 | 1 |
| Race (NIH/OMB)(Participants) | Targeted Epidural Patching of CSF Leaks With Autologous Blood and Fibrin Glue | Simulated Patching Procedure | Total |
|---|---|---|---|
| American Indian or Alaska Native | 1 | 0 | 1 |
| Asian | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 3 | 2 | 5 |
| White | 3 | 4 | 7 |
| More than one race | 0 | 1 | 1 |
| Unknown or Not Reported | 1 | 0 | 1 |
| Region of Enrollment(Participants) | Targeted Epidural Patching of CSF Leaks With Autologous Blood and Fibrin Glue | Simulated Patching Procedure | Total |
|---|---|---|---|
| United States | 8 | 7 | 15 |
PDFs hosted by the registry, ClinicalTrials.gov.
Ran from Dec 2017 to primary completion in Mar 2020, 27 months.
Results were first posted in Jun 2021, 1 year 2 months after primary completion.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in May 2021. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions 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.
Studies of the drug tested here: Fibrin Tissue Adhesive