Sickle Cell DiseasePhase 1NCT02012777
Propanolol and Red Cell Adhesion Non-asthmatic Children Sickle Cell Disease
A Phase 1 study testing propranolol in people with Sickle Cell Disease, run by University of Miami at 1 site in United States.
Trial summary
Propanolol is a beta blocker which has been found to inhibit the ability of epinephrine to upregulate sickle red cell adhesion to laminin and endothelial cells in vitro. The purpose of this pilot study is to administer one dose of propanolol to children with sickle cell disease and to measure pre and post dose red… Read more about this study
- Who is it for?
- Ages 10 to 17 years
- Conditions the study is for
- Sickle Cell Disease
- What is being tested?
- propranolol
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2010to 3 Apr 2013
- Phase
- Phase 1
- 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 10 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- diagnosis of HbSS or HbSBeta0Thal
- age 10-17 years
- Weight 30kg or greater
- Hb 7mg/dL or greater
- informed consent
Who cannot join
- History of vaso-occlusive crisis during the past 6 weeks, or history of transfusion during the past 3 months.
- pregnancy
- history of heart failure, myocardial infarction, asthma, bradyarrythmias, hypotension, thyroid disease, diabetes, renal insufficiency
- concurrent medications: any antihypertensive medication, diuretics, thyroid replacement medications, any arrythmia medication, insulin, hypoglycaemic medication
- history of allergy to sulfonamides
- elevated BUN or creatinine
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Propanolol Effect on Red Cell Adhesion in Non-Asthmatic Children With Sickle Cell Disease: A Dose Finding Study
Propanolol is a beta blocker which has been found to inhibit the ability of epinephrine to upregulate sickle red cell adhesion to laminin and endothelial cells in vitro. The purpose of this pilot study is to administer one dose of propanolol to children with sickle cell disease and to measure pre and post dose red cell adhesion. The hypothesis is that a single dose of propanolol will decrease red cell adhesion to laminin and endothelial cells as compared to baseline.
Read the detailed description
A similar pilot study has already been conducted in adults and is now being tried in children to gather preliminary data for a grant submission. No safety issues were found in the adult pilot study. This study will evaluate the effect of different doses of propanolol. The risks of this study involve the risks of three (3) blood draws and the risks of propanolol. In order to minimize the risks children with sickle cell disease and asthma will be excluded because asthma is a contraindication to the use of propanolol. In addition, patients will not be hypertensive or bradycardic.
- Conditions
- Sickle Cell Disease
- Being tested
- propranolol
- Keywords
- sickle cell disease, propanolol, red blood cell adhesion
- Medical subject headings
- Anemia, Sickle Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
propranololDrug
Also called propanolol systemic, Inderal, Inderal LA, InnoPran XL
Propranolol hydrochloride is a synthetic beta-adrenergic receptor-blocking agent. This will be administered in an open-label single administration to 3 cohorts (10mg, 20mg, and 40mg) of children with sickle cell disease. Patient blood will be evaluated for red cell adhesion and patient data evaluated for safety monitoring.
| Study group | Role | What they receive |
|---|---|---|
| cohort 1 10mg propranolol | Active comparator | first study arm will consist of 5 subjects who will be administered a dose of 10mg propanolol and followed 1-4 weeks.
Data safety and monitoring committee has reviewed the data for safety and instructed the study to continue based on the findings. Receives: Drug: propranolol |
| cohort 2 20mg propranolol | Active comparator | This cohort will involve the administration of 5 subjects with 20mg propanolol. The data safety and monitoring committee will review the data for safety when the 5 subjects are recruited and instruct the study to continue depending on the findings. Receives: Drug: propranolol |
| cohort 3 40mg propranolol | Active comparator | This cohort will involve the administration of 10 subjects with 40mg propanolol. The data safety and monitoring committee will review the data for safety when the 10 subjects are recruited and instruct the study to continue depending on the findings. Receives: Drug: propranolol |
What is being measured
The primary outcome is the main question the study is designed to answer.
measurement of the sickle red cell response to epinephrine
At study initiation 5mL of blood is drawn to evaluate for red cell adhesion (screening visit or visit 1). At the intervention visit 1-4 weeks later another 5mL of blood will be drawn and patient will have an ECG performed, followed by one dose of propanolol at the stratum that s/he is in. Vitals signs will be monitored (including blood pressure) for 4 hours after drug administration.
Measured: 1-4 weeks
Secondary outcomes (1)
Safety data regarding the use of propanolol in children with sickle cell disease
- New onset wheezing
- Onset of low blood pressure defined as blood pressure less than 90/50
- Onset of heart rate less than 60 beats/min
Measured: within 24 hours after drug administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Dec 2013 (estimated)
- Study startJun 2010
- Primary completionNov 2012
- Study completion3 Apr 2013
Why it stopped: Inability to recruit patients into the study.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
- More trials run by University of MiamiThe 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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Miami
- Sponsor type
- University, hospital or other
- Collaborators
- Duke University
- Responsible party
- Principal investigator, Ofelia Alvarez, University of Miami
- Investigators
- Ofelia A Alvarez, MD, Principal investigator, University of Miami
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02012777
- Sponsor's protocol ID
- 20100334
- Status last verified
- Jun 2017
- First submitted
- 6 Dec 2013
- Last updated
- 8 Jun 2017
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes
Publications
Storch CH, Hoeger PH. Propranolol for infantile haemangiomas: insights into the molecular mechanisms of action. Br J Dermatol. 2010 Aug;163(2):269-74. doi: 10.1111/j.1365-2133.2010.09848.x. Epub 2010 May 8.
PubMed 20456345Leaute-Labreze C, Dumas de la Roque E, Hubiche T, Boralevi F, Thambo JB, Taieb A. Propranolol for severe hemangiomas of infancy. N Engl J Med. 2008 Jun 12;358(24):2649-51. doi: 10.1056/NEJMc0708819. No abstract available.
PubMed 18550886Lawley LP, Siegfried E, Todd JL. Propranolol treatment for hemangioma of infancy: risks and recommendations. Pediatr Dermatol. 2009 Sep-Oct;26(5):610-4. doi: 10.1111/j.1525-1470.2009.00975.x.
PubMed 19840322Zimmermann AP, Wiegand S, Werner JA, Eivazi B. Propranolol therapy for infantile haemangiomas: review of the literature. Int J Pediatr Otorhinolaryngol. 2010 Apr;74(4):338-42. doi: 10.1016/j.ijporl.2010.01.001. Epub 2010 Feb 1.
PubMed 20117846Lamy S, Lachambre MP, Lord-Dufour S, Beliveau R. Propranolol suppresses angiogenesis in vitro: inhibition of proliferation, migration, and differentiation of endothelial cells. Vascul Pharmacol. 2010 Nov-Dec;53(5-6):200-8. doi: 10.1016/j.vph.2010.08.002. Epub 2010 Aug 20.
PubMed 20732454Holmes WJ, Mishra A, Gorst C, Liew SH. Propranolol as first-line treatment for rapidly proliferating infantile haemangiomas. J Plast Reconstr Aesthet Surg. 2011 Apr;64(4):445-51. doi: 10.1016/j.bjps.2010.07.009. Epub 2010 Aug 24.
PubMed 20797926Schiestl C, Neuhaus K, Zoller S, Subotic U, Forster-Kuebler I, Michels R, Balmer C, Weibel L. Efficacy and safety of propranolol as first-line treatment for infantile hemangiomas. Eur J Pediatr. 2011 Apr;170(4):493-501. doi: 10.1007/s00431-010-1324-2. Epub 2010 Oct 9.
PubMed 20936416Chang, MW. Journal Watch Dermatology. Nov 6, 2009 Propanolol for Infantile Hemangioma: Safety Issues and Proposed Protocol
Holland KE, Frieden IJ, Frommelt PC, Mancini AJ, Wyatt D, Drolet BA. Hypoglycemia in children taking propranolol for the treatment of infantile hemangioma. Arch Dermatol. 2010 Jul;146(7):775-8. doi: 10.1001/archdermatol.2010.158.
PubMed 20644039
Study at a glance
From the registry record, last updated by the sponsor on 8 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Propanolol Effect on Red Cell Adhesion in Non-Asthmatic Children With Sickle Cell Disease: A Dose Finding Study
- ClinicalTrials.gov ID
- NCT02012777
- Acronym / sponsor ID
- 20100334
- Conditions
- Sickle Cell Disease
- Keywords
- sickle cell disease, propanolol, red blood cell adhesion
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Inability to recruit patients into the study.
- Enrolment
- 9 participants (actual)
- Lead sponsor
- University of MiamiUniversity, hospital or other
- Collaborators
- Duke University
- Study start
- Jun 2010
- Primary completion
- Nov 2012 (actual)
- Study completion
- 3 Apr 2013 (actual)
- First posted
- 16 Dec 2013 (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.
Propanolol is a beta blocker which has been found to inhibit the ability of epinephrine to upregulate sickle red cell adhesion to laminin and endothelial cells in vitro. The purpose of this pilot study is to administer one dose of propanolol to children with sickle cell disease and to measure pre and post dose red cell adhesion. The hypothesis is that a single dose of propanolol will decrease red cell adhesion to laminin and endothelial cells as compared to baseline.
Detailed description
A similar pilot study has already been conducted in adults and is now being tried in children to gather preliminary data for a grant submission. No safety issues were found in the adult pilot study. This study will evaluate the effect of different doses of propanolol. The risks of this study involve the risks of three (3) blood draws and the risks of propanolol. In order to minimize the risks children with sickle cell disease and asthma will be excluded because asthma is a contraindication to the use of propanolol. In addition, patients will not be hypertensive or bradycardic.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| cohort 1 10mg propranolol | Active comparator | Drug: propranololfirst study arm will consist of 5 subjects who will be administered a dose of 10mg propanolol and followed 1-4 weeks. Data safety and monitoring committee has reviewed the data for safety and instructed the study to continue based on the findings. |
| cohort 2 20mg propranolol | Active comparator | Drug: propranololThis cohort will involve the administration of 5 subjects with 20mg propanolol. The data safety and monitoring committee will review the data for safety when the 5 subjects are recruited and instruct the study to continue depending on the findings. |
| cohort 3 40mg propranolol | Active comparator | Drug: propranololThis cohort will involve the administration of 10 subjects with 40mg propanolol. The data safety and monitoring committee will review the data for safety when the 10 subjects are recruited and instruct the study to continue depending on the findings. |
Who may qualify
- Ages
- 10 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- diagnosis of HbSS or HbSBeta0Thal
- age 10-17 years
- Weight 30kg or greater
- Hb 7mg/dL or greater
- informed consent
Key exclusion criteria (6 listed)
- History of vaso-occlusive crisis during the past 6 weeks, or history of transfusion during the past 3 months.
- pregnancy
- history of heart failure, myocardial infarction, asthma, bradyarrythmias, hypotension, thyroid disease, diabetes, renal insufficiency
- concurrent medications: any antihypertensive medication, diuretics, thyroid replacement medications, any arrythmia medication, insulin, hypoglycaemic medication
- history of allergy to sulfonamides
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 |
|---|---|---|
| propranololAlso: propanolol systemic, Inderal, Inderal LA, InnoPran XLPropranolol hydrochloride is a synthetic beta-adrenergic receptor-blocking agent. This will be administered in an open-label single administration to 3 cohorts (10mg, 20mg, and 40mg) of children with sickle cell disease. Patient blood will be evaluated for red cell adhesion and patient data evaluated for safety monitoring. | Drug | cohort 1 10mg propranolol, cohort 2 20mg propranolol, cohort 3 40mg propranolol |
Primary outcome
measurement of the sickle red cell response to epinephrine
Time frame: 1-4 weeks
At study initiation 5mL of blood is drawn to evaluate for red cell adhesion (screening visit or visit 1). At the intervention visit 1-4 weeks later another 5mL of blood will be drawn and patient will have an ECG performed, followed by one dose of propanolol at the stratum that s/he is in. Vitals signs will be monitored (including blood pressure) for 4 hours after drug administration.
1 secondary outcome
Safety data regarding the use of propanolol in children with sickle cell disease
Time frame: within 24 hours after drug administration
Results and safety
The study was stopped early (reason given: Inability to recruit patients into the study.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jun 2017.
- Background: PubMed 20456345Storch CH, Hoeger PH. Propranolol for infantile haemangiomas: insights into the molecular mechanisms of action. Br J Dermatol. 2010 Aug;163(2):269-74. doi: 10.1111/j.1365-2133.2010.09848.x. Epub 2010 May 8.
- Results publication: PubMed 18550886Leaute-Labreze C, Dumas de la Roque E, Hubiche T, Boralevi F, Thambo JB, Taieb A. Propranolol for severe hemangiomas of infancy. N Engl J Med. 2008 Jun 12;358(24):2649-51. doi: 10.1056/NEJMc0708819. No abstract available.
- Results publication: PubMed 19840322Lawley LP, Siegfried E, Todd JL. Propranolol treatment for hemangioma of infancy: risks and recommendations. Pediatr Dermatol. 2009 Sep-Oct;26(5):610-4. doi: 10.1111/j.1525-1470.2009.00975.x.
- Results publication: PubMed 20117846Zimmermann AP, Wiegand S, Werner JA, Eivazi B. Propranolol therapy for infantile haemangiomas: review of the literature. Int J Pediatr Otorhinolaryngol. 2010 Apr;74(4):338-42. doi: 10.1016/j.ijporl.2010.01.001. Epub 2010 Feb 1.
- Results publication: PubMed 20732454Lamy S, Lachambre MP, Lord-Dufour S, Beliveau R. Propranolol suppresses angiogenesis in vitro: inhibition of proliferation, migration, and differentiation of endothelial cells. Vascul Pharmacol. 2010 Nov-Dec;53(5-6):200-8. doi: 10.1016/j.vph.2010.08.002. Epub 2010 Aug 20.
- Results publication: PubMed 20797926Holmes WJ, Mishra A, Gorst C, Liew SH. Propranolol as first-line treatment for rapidly proliferating infantile haemangiomas. J Plast Reconstr Aesthet Surg. 2011 Apr;64(4):445-51. doi: 10.1016/j.bjps.2010.07.009. Epub 2010 Aug 24.
- Results publication: PubMed 20936416Schiestl C, Neuhaus K, Zoller S, Subotic U, Forster-Kuebler I, Michels R, Balmer C, Weibel L. Efficacy and safety of propranolol as first-line treatment for infantile hemangiomas. Eur J Pediatr. 2011 Apr;170(4):493-501. doi: 10.1007/s00431-010-1324-2. Epub 2010 Oct 9.
- Results publicationChang, MW. Journal Watch Dermatology. Nov 6, 2009 Propanolol for Infantile Hemangioma: Safety Issues and Proposed Protocol
- Results publication: PubMed 20644039Holland KE, Frieden IJ, Frommelt PC, Mancini AJ, Wyatt D, Drolet BA. Hypoglycemia in children taking propranolol for the treatment of infantile hemangioma. Arch Dermatol. 2010 Jul;146(7):775-8. doi: 10.1001/archdermatol.2010.158.
- Individual participant dataSharing planned: Yes
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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.
Ofelia A Alvarez, MD principal investigator
University of Miami
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing propranolol in people with Sickle Cell Disease, run by University of Miami 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 6 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: stopped early, as of the sponsor's last update on 8 Jun 2017. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 was stopped early (reason given: Inability to recruit patients into the study.). Results are not available in the source record.
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.
What does the primary outcome measure?
measurement of the sickle red cell response to epinephrine (time frame: 1-4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02012777, which also lists 9 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 8 Jun 2017; AzTrials last refreshed its copy on 6 Nov 2026.