Evaluation of the Efficacy, Safety, and Tolerability of Sarizotan in Rett Syndrome With Respiratory Symptoms (STARS)

• ClinicalTrials.gov Identifier: NCT02790034
• Recruitment Status: Terminated
• First Posted: June 3, 2016
• Results First Posted: December 21, 2021
• Last Update Posted: December 21, 2021
• Sponsor: Newron Pharmaceuticals SPA
• Information provided by (Responsible Party): Newron Pharmaceuticals SPA

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Rett Syndrome
• Interventions: Drug: Sarizotan low dose; Drug: Sarizotan high dose; Drug: Placebo
• Enrollment: 129

Participant Flow

Recruitment Details

The study was conducted at 14 sites in 5 countries. Enrollment occurred from 26-Oct-2016 through February 2019 . An analysis was planned when the primary efficacy data at Week 24 were available for all patients (06 August 2019 - last patient last visit for double-blind part of the study). Patients without safety and tolerability issues continued in the open label with sarizotan for an additional 24 weeks and then another 48 weeks if no safety issues were present.

Pre-assignment Details

A total of 198 patients were screened, of which 69 (34.8%) patients were screen failures. A total of 129 patients were randomized in the study. A total of 128 patients were exposed to at least one dose of IMP, with placebo ITT group (40) vs safety pop (39).

Arm/Group Title	Sarizotan Low Dose	Sarizotan High Dose	Placebo
Arm/Group Description	2 mg or 5 mg bid based on age and weight criteria for 24 wks DB 2 mg bid (4 to <13 years; ≥13 years of age and weighing <25 kg 5 mg bid (≥13 years of age and weighing ≥25 kg)	5 mg or 10 mg bid based on age and weight criteria for 24 wks DB 5 mg bid (4 to <13 years; ≥13 years of age and weighing <25 kg 10 mg bid (≥13 years of age and weighing ≥25 kg)	Placebo bid for 24 wks DB
Period Title: Overall Study
Started	33	56	40
Completed	27	46	36
Not Completed	6	10	4

Baseline Characteristics

Arm/Group Title		Sarizotan Low Dose	Sarizotan High Dose	Placebo	Total
Arm/Group Description		2 mg or 5 mg bid based on age and weight criteria for 24 wks DB 2 mg bid (4 to <13 years; ≥13 years of age and weighing <25 kg 5 mg bid (≥13 years of age and weighing ≥25 kg)	5 mg or 10 mg bid based on age and weight criteria for 24 wks DB 5 mg bid (4 to <13 years; ≥13 years of age and weighing <25 kg 10 mg bid (≥13 years of age and weighing ≥25 kg)	Placebo BID	Total of all reporting groups
Overall Number of Baseline Participants		33	56	40	129
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	33 participants	56 participants	40 participants	129 participants
	<=18 years	23 69.7%	35 62.5%	27 67.5%	85 65.9%
	Between 18 and 65 years	10 30.3%	21 37.5%	13 32.5%	44 34.1%
	>=65 years	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	33 participants	56 participants	40 participants	129 participants
		13.23 (7.195)	15.55 (9.362)	14.13 (9.155)	14.51 (8.780)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	33 participants	56 participants	40 participants	129 participants
	Female	33 100.0%	56 100.0%	40 100.0%	129 100.0%
	Male	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	33 participants	56 participants	40 participants	129 participants
	Hispanic or Latino	4 12.1%	5 8.9%	4 10.0%	13 10.1%
	Not Hispanic or Latino	29 87.9%	51 91.1%	36 90.0%	116 89.9%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	33 participants	56 participants	40 participants	129 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Asian	8 24.2%	16 28.6%	13 32.5%	37 28.7%
	Native Hawaiian or Other Pacific Islander	0 0.0%	1 1.8%	0 0.0%	1 0.8%
	Black or African American	1 3.0%	1 1.8%	3 7.5%	5 3.9%
	White	23 69.7%	37 66.1%	22 55.0%	82 63.6%
	More than one race	1 3.0%	0 0.0%	0 0.0%	1 0.8%
	Unknown or Not Reported	0 0.0%	1 1.8%	2 5.0%	3 2.3%
Region of Enrollment; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	33 participants	56 participants	40 participants	129 participants
United States		11 33.3%	19 33.9%	11 27.5%	41 31.8%
Italy		8 24.2%	13 23.2%	9 22.5%	30 23.3%
United Kingdom		5 15.2%	10 17.9%	6 15.0%	21 16.3%
Australia		1 3.0%	0 0.0%	2 5.0%	3 2.3%
India		8 24.2%	14 25.0%	12 30.0%	34 26.4%
Duration of Rett syndrome; Mean (Standard Deviation); Unit of measure: Months
	Number Analyzed	33 participants	56 participants	40 participants	129 participants
		87.90 (72.536)	97.18 (72.922)	73.94 (65.800)	87.94 (70.696)

Outcome Measures

1. Primary Outcome

Title	Reduction in Respiratory Abnormality in Patients With Rett Syndrome
Description	Measured as the percent change in the number of apnea episodes per hour during awake time, calculated using an ambulatory data acquisition system (BioRadioTM) as part of home monitoring procedure. BioRadioTM record specific respiratory and cardiac parameters.
Time Frame	Baseline up to week 24

Outcome Measure Data

Analysis Population Description

The ITT population included all patients who were randomized to treatment. This population was used for all efficacy analysis.

Arm/Group Title	Sarizotan Low Dose	Sarizotan High Dose	Placebo
Arm/Group Description:	2 mg or 5 mg bid based on age and weight criteria for 24 wks DB 2 mg bid (4 to <13 years; ≥13 years of age and weighing <25 kg 5 mg bid (≥13 years of age and weighing ≥25 kg)	5 mg or 10 mg bid based on age and weight criteria for 24 wks DB 5 mg bid (4 to <13 years; ≥13 years of age and weighing <25 kg 10 mg bid (≥13 years of age and weighing ≥25 kg)	Placebo BID
Overall Number of Participants Analyzed	33	56	40
Least Squares Mean (Standard Error); Unit of Measure: % of change in mean counts per hr
	1.54 (10.1228)	13.211 (7.5075)	18.503 (8.441)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sarizotan High Dose, Placebo
	Comments	Primary inferential comparison between treatment groups used a restricted maximum likelihood (REML)-based, mixed-effects repeated measures model approach (MMRM) with 95% CI for the difference between treatment groups for % change from baseline in the number of apnea episodes. Model included % change from baseline as response, the fixed, categorical effects of treatment group, visit, treatment group-by-visit interaction, and the continuous terms age and baseline value as covariate.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.6411
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-5.292
	Confidence Interval	(2-Sided) 95%; -27.741 to 17.157
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 11.3184
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Sarizotan Low Dose, Placebo
	Comments	Primary inferential comparison between treatment groups used a restricted maximum likelihood (REML)-based, mixed-effects repeated measures model approach (MMRM) with 95% CI for the difference between treatment groups for % change from baseline in the number of apnea episodes. Model included % change from baseline as response, the fixed, categorical effects of treatment group, visit, treatment group-by-visit interaction, and the continuous terms age and baseline value as covariate.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.2011
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-16.966
	Confidence Interval	(2-Sided) 95%; -43.119 to 9.186
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 13.1869
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Efficacy of Sarizotan Assessed by the Caregiver-rated Impression of Change
Description	Caregiver-rated Impression of Change (CIC): 7-point scale requiring the caregiver to rate how much the patient's illness has improved or worsened relative to the baseline state. 7-point Likert-type scale for which ratings range from 1 = very much improved to 7 = very much worse, with 4 = no change. This caregiver-rated measure considered activities, behavior, mood and functioning. This rating was performed in consultation with the study Investigator but was based largely on the caregivers' evaluation during the reporting period. The single rating of the CIC was to be based on changes in the following domains: • Activities (watching TV, interest in conversations around her, cooperation during toileting, dressing/bathing, etc.), • Communication (verbal or by eye movements, hand movements, or head movements), • Behavior (agitation, refusal to feed, scratching, social avoidance), • Participation in family/outdoor/social events)
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

The ITT population included all patients who were randomized to treatment. This population was used for all efficacy analysis.

Arm/Group Title	Sarizotan Low Dose	Sarizotan High Dose	Placebo
Arm/Group Description:	2 mg or 5 mg bid based on age and weight criteria for 24 wks DB 2 mg bid (4 to <13 years; ≥13 years of age and weighing <25 kg 5 mg bid (≥13 years of age and weighing ≥25 kg)	5 mg or 10 mg bid based on age and weight criteria for 24 wks DB 5 mg bid (4 to <13 years; ≥13 years of age and weighing <25 kg 10 mg bid (≥13 years of age and weighing ≥25 kg)	Placebo BID
Overall Number of Participants Analyzed	33	56	40
Mean (Standard Deviation); Unit of Measure: score on a scale
	3.6 (0.67)	3.5 (1.12)	3.4 (0.79)

Adverse Events

Time Frame	AEs will be collected, from the time of signing of Informed Consent to the end of the safety follow-up period (14 days after last dose of study medication at 24 weeks). In addition, all subjects will be followed up for 30 days after last dose for SAEs, up to a total of 28 weeks.
Adverse Event Reporting Description	Analysis population = safety population defined as all patients randomized and exposed to at least one dose of IMP. One patient randomized to placebo treatment did not receive IMP, hence placebo ITT group (40) vs safety pop (39). Classification of the Event: Classify the event as either serious or non-serious Description of Signs or Symptoms: Whenever possible, record a specific diagnosis for the event Start/stop date Intensity (mild, moderate, severe) Causality Action taken with IMP
Arm/Group Title	Sarizotan Low Dose		Sarizotan High Dose		Placebo
Arm/Group Description	2 mg or 5 mg bid based on age and weight criteria for 24 wks DB 2 mg bid (4 to <13 years; ≥13 years of age and weighing <25 kg 5 mg bid (≥13 years of age and weighing ≥25 kg) Assessment of safety, tolerability and efficacy on reducing the respiratory symptoms in patients.		5 mg or 10 mg bid based on age and weight criteria for 24 wks DB 5 mg bid (4 to <13 years; ≥13 years of age and weighing <25 kg 10 mg bid (≥13 years of age and weighing ≥25 kg) Assessment of safety, tolerability and efficacy on reducing the respiratory symptoms in patients.		Placebo bid respectively Placebo: placebo BID followed by assessment of safety, tolerability and efficacy on reducing the respiratory symptoms in patients.
All-Cause Mortality
	Sarizotan Low Dose		Sarizotan High Dose		Placebo
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	0/33 (0.00%)		0/56 (0.00%)		0/39 (0.00%)
Serious Adverse Events
	Sarizotan Low Dose		Sarizotan High Dose		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/33 (6.06%)		10/56 (17.86%)		5/39 (12.82%)
Blood and lymphatic system disorders
Neutropenia † 1	0/33 (0.00%)		1/56 (1.79%)	1	0/39 (0.00%)
Gastrointestinal disorders
Gingival Hypertrophy † 1	1/33 (3.03%)	1	0/56 (0.00%)		0/39 (0.00%)
Constipation † 1	0/33 (0.00%)		1/56 (1.79%)	1	0/39 (0.00%)
Infections and infestations
Lower respiratory tract infection † 1	1/33 (3.03%)	1	1/56 (1.79%)	1	0/39 (0.00%)
Gingivitis † 1	1/33 (3.03%)	1	0/56 (0.00%)		0/39 (0.00%)
Lower respiratory tract infection bacterial † 1	0/33 (0.00%)		1/56 (1.79%)	1	0/39 (0.00%)
Pneumonia † 1	0/33 (0.00%)		1/56 (1.79%)	1	0/39 (0.00%)
Injury, poisoning and procedural complications
Medication error † 1	0/33 (0.00%)		1/56 (1.79%)	1	1/39 (2.56%)	1
Accidental Overdose † 1	0/33 (0.00%)		0/56 (0.00%)		2/39 (5.13%)	2
Femur Fracture † 1	0/33 (0.00%)		0/56 (0.00%)		1/39 (2.56%)	1
Investigations
Electrocardiogram QT prolonged † 1	0/33 (0.00%)		1/56 (1.79%)	1	1/39 (2.56%)	1
Metabolism and nutrition disorders
Hyponatraemia † 1	0/33 (0.00%)		1/56 (1.79%)	1	0/39 (0.00%)
Hypophagia † 1	0/33 (0.00%)		1/56 (1.79%)	1	0/39 (0.00%)
Nervous system disorders
Seizure † 1	1/33 (3.03%)	1	0/56 (0.00%)		0/39 (0.00%)
Somnolence † 1	0/33 (0.00%)		2/56 (3.57%)	2	1/39 (2.56%)	1
Change in seizure presentation † 1	0/33 (0.00%)		1/56 (1.79%)	1	0/39 (0.00%)
Generalised tonic-clonic seizure † 1	0/33 (0.00%)		1/56 (1.79%)	1	0/39 (0.00%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory Failure † 1	0/33 (0.00%)		1/56 (1.79%)	1	0/39 (0.00%)
Asthma † 1	0/33 (0.00%)		1/56 (1.79%)	1	0/39 (0.00%)
1 Term from vocabulary, MedDRA 22.0; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Sarizotan Low Dose		Sarizotan High Dose		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	25/33 (75.76%)		46/56 (82.14%)		30/39 (76.92%)
Gastrointestinal disorders
Diarrhoea † 1	2/33 (6.06%)	2	4/56 (7.14%)	4	4/39 (10.26%)	4
Constipation † 1	2/33 (6.06%)	2	5/56 (8.93%)	5	2/39 (5.13%)	2
Vomiting † 1	5/33 (15.15%)	5	2/56 (3.57%)	2	2/39 (5.13%)	2
General disorders
Pyrexia † 1	4/33 (12.12%)	4	3/56 (5.36%)	3	0/39 (0.00%)
Infections and infestations
Urinary Tract Infection † 1	2/33 (6.06%)	2	3/56 (5.36%)	3	3/39 (7.69%)	3
Upper respiratory tract infection † 1	1/33 (3.03%)	1	5/56 (8.93%)	5	1/39 (2.56%)	1
Nervous system disorders
Seizure † 1	8/33 (24.24%)	8	15/56 (26.79%)	15	5/39 (12.82%)	5
Somnolence † 1	2/33 (6.06%)	2	10/56 (17.86%)	10	6/39 (15.38%)	6
Psychomotor hyperactivity † 1	4/33 (12.12%)	4	1/56 (1.79%)	1	3/39 (7.69%)	3
Dystonia † 1	3/33 (9.09%)	3	3/56 (5.36%)	3	1/39 (2.56%)	1
Psychiatric disorders
Sleep Disorder † 1	3/33 (9.09%)	3	4/56 (7.14%)	4	1/39 (2.56%)	1
Insomnia † 1	3/33 (9.09%)	3	2/56 (3.57%)	2	2/39 (5.13%)	2
Respiratory, thoracic and mediastinal disorders
Cough † 1	1/33 (3.03%)	1	3/56 (5.36%)	3	4/39 (10.26%)	4
1 Term from vocabulary, MedDRA 22.0; † Indicates events were collected by systematic assessment

Limitations and Caveats

No efficacy evaluation was performed for the open label extension, as the study was terminated prematurely by the Sponsor based on lack of demonstrated efficacy in the double-blind period.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

 

Results Point of Contact

• Name/Title: Ravi Anand MD, Chief Medical Officer
• Organization: Newron Pharmaceuticals S.p.A.
• Phone: +41 793741364
• EMail: regulatoryaffairs@newron.com

Publications:

Abdala AP, Dutschmann M, Bissonnette JM, Paton JF. Correction of respiratory disorders in a mouse model of Rett syndrome. Proc Natl Acad Sci U S A. 2010 Oct 19;107(42):18208-13. doi: 10.1073/pnas.1012104107. Epub 2010 Oct 4.

Abdala AP, Bissonnette JM, Newman-Tancredi A. Pinpointing brainstem mechanisms responsible for autonomic dysfunction in Rett syndrome: therapeutic perspectives for 5-HT1A agonists. Front Physiol. 2014 May 30;5:205. doi: 10.3389/fphys.2014.00205. eCollection 2014.

Abdala AP, Lioy DT, Garg SK, Knopp SJ, Paton JF, Bissonnette JM. Effect of Sarizotan, a 5-HT1a and D2-like receptor agonist, on respiration in three mouse models of Rett syndrome. Am J Respir Cell Mol Biol. 2014 Jun;50(6):1031-9. doi: 10.1165/rcmb.2013-0372OC.

Adams JA, Zabaleta IA, Stroh D, Sackner MA. Measurement of breath amplitudes: comparison of three noninvasive respiratory monitors to integrated pneumotachograph. Pediatr Pulmonol. 1993 Oct;16(4):254-8. doi: 10.1002/ppul.1950160408.

Bloch KE, Li Y, Sackner MA, Russi EW. Breathing pattern during sleep disruptive snoring. Eur Respir J. 1997 Mar;10(3):576-86.

Brouillette RT, Morrow AS, Weese-Mayer DE, Hunt CE. Comparison of respiratory inductive plethysmography and thoracic impedance for apnea monitoring. J Pediatr. 1987 Sep;111(3):377-83. doi: 10.1016/s0022-3476(87)80457-2.

Byard RW. Forensic issues and possible mechanisms of sudden death in Rett syndrome. J Clin Forensic Med. 2006 Feb;13(2):96-9. doi: 10.1016/j.jcfm.2005.08.013. Epub 2005 Nov 2.

Cantineau JP, Escourrou P, Sartene R, Gaultier C, Goldman M. Accuracy of respiratory inductive plethysmography during wakefulness and sleep in patients with obstructive sleep apnea. Chest. 1992 Oct;102(4):1145-51. doi: 10.1378/chest.102.4.1145.

Clarenbach CF, Senn O, Brack T, Kohler M, Bloch KE. Monitoring of ventilation during exercise by a portable respiratory inductive plethysmograph. Chest. 2005 Sep;128(3):1282-90. doi: 10.1378/chest.128.3.1282.

Collop NA, Anderson WM, Boehlecke B, Claman D, Goldberg R, Gottlieb DJ, Hudgel D, Sateia M, Schwab R; Portable Monitoring Task Force of the American Academy of Sleep Medicine. Clinical guidelines for the use of unattended portable monitors in the diagnosis of obstructive sleep apnea in adult patients. Portable Monitoring Task Force of the American Academy of Sleep Medicine. J Clin Sleep Med. 2007 Dec 15;3(7):737-47.

Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0, May 28, 2009 (v4.03 June 14, 2010), U.S. Department of Health and Human Services.

FitzGerald PM, Jankovic J, Percy AK. Rett syndrome and associated movement disorders. Mov Disord. 1990;5(3):195-202. doi: 10.1002/mds.870050303.

Guy W (Ed). Clinical Global Impressions. In ECDEU Assessment Manual for Psychopharmacology, revised, U.S. Department of Health, Education and Welfare Pub. No. (ADM) 76-338. Rockville, MD: NIMH, 1976, 217-222.

Hammer J, Newth CJ, Deakers TW. Validation of the phase angle technique as an objective measure of upper airway obstruction. Pediatr Pulmonol. 1995 Mar;19(3):167-73. doi: 10.1002/ppul.1950190305.

Julu PO, Kerr AM, Hansen S, Apartopoulos F, Jamal GA. Immaturity of medullary cardiorespiratory neurones leading to inappropriate autonomic reactions as a likely cause of sudden death in Rett's syndrome. Arch Dis Child. 1997 Nov;77(5):464-5. doi: 10.1136/adc.77.5.463c. No abstract available.

Julu PO, Kerr AM, Apartopoulos F, Al-Rawas S, Engerstrom IW, Engerstrom L, Jamal GA, Hansen S. Characterisation of breathing and associated central autonomic dysfunction in the Rett disorder. Arch Dis Child. 2001 Jul;85(1):29-37. doi: 10.1136/adc.85.1.29.

Julu PO, Engerstrom IW, Hansen S, Apartopoulos F, Engerstrom B, Pini G, Delamont RS, Smeets EE. Cardiorespiratory challenges in Rett's syndrome. Lancet. 2008 Jun 14;371(9629):1981-3. doi: 10.1016/S0140-6736(08)60849-1. No abstract available.

Katz DM, Dutschmann M, Ramirez JM, Hilaire G. Breathing disorders in Rett syndrome: progressive neurochemical dysfunction in the respiratory network after birth. Respir Physiol Neurobiol. 2009 Aug 31;168(1-2):101-8. doi: 10.1016/j.resp.2009.04.017. Epub 2009 Apr 24.

Kerr AM, Armstrong DD, Prescott RJ, Doyle D, Kearney DL. Rett syndrome: analysis of deaths in the British survey. Eur Child Adolesc Psychiatry. 1997;6 Suppl 1:71-4.

Khwaja OS, Ho E, Barnes KV, O'Leary HM, Pereira LM, Finkelstein Y, Nelson CA 3rd, Vogel-Farley V, DeGregorio G, Holm IA, Khatwa U, Kapur K, Alexander ME, Finnegan DM, Cantwell NG, Walco AC, Rappaport L, Gregas M, Fichorova RN, Shannon MW, Sur M, Kaufmann WE. Safety, pharmacokinetics, and preliminary assessment of efficacy of mecasermin (recombinant human IGF-1) for the treatment of Rett syndrome. Proc Natl Acad Sci U S A. 2014 Mar 25;111(12):4596-601. doi: 10.1073/pnas.1311141111. Epub 2014 Mar 12.

Konno K, Mead J. Measurement of the separate volume changes of rib cage and abdomen during breathing. J Appl Physiol. 1967 Mar;22(3):407-22. doi: 10.1152/jappl.1967.22.3.407. No abstract available.

Landon C. Respiratory monitoring: Advantages of inductive plethysmography over impedance pneumograpy. VivoMetrics, VMLA-039-02, 2003.

Leino K, Nunes S, Valta P, Takala J. Validation of a new respiratory inductive plethysmograph. Acta Anaesthesiol Scand. 2001 Jan;45(1):104-11. doi: 10.1034/j.1399-6576.2001.450116.x.

Loube DI, Andrada T, Howard RS. Accuracy of respiratory inductive plethysmography for the diagnosis of upper airway resistance syndrome. Chest. 1999 May;115(5):1333-7. doi: 10.1378/chest.115.5.1333.

Neul JL, Fang P, Barrish J, Lane J, Caeg EB, Smith EO, Zoghbi H, Percy A, Glaze DG. Specific mutations in methyl-CpG-binding protein 2 confer different severity in Rett syndrome. Neurology. 2008 Apr 15;70(16):1313-21. doi: 10.1212/01.wnl.0000291011.54508.aa. Epub 2008 Mar 12.

Neul JL, Kaufmann WE, Glaze DG, Christodoulou J, Clarke AJ, Bahi-Buisson N, Leonard H, Bailey ME, Schanen NC, Zappella M, Renieri A, Huppke P, Percy AK; RettSearch Consortium. Rett syndrome: revised diagnostic criteria and nomenclature. Ann Neurol. 2010 Dec;68(6):944-50. doi: 10.1002/ana.22124.

Neul JL, Glaze DG, Percy AK, Feyma T, Beisang A, Dinh T, Suter B, Anagnostou E, Snape M, Horrigan J, Jones NE. Improving Treatment Trial Outcomes for Rett Syndrome: The Development of Rett-specific Anchors for the Clinical Global Impression Scale. J Child Neurol. 2015 Nov;30(13):1743-8. doi: 10.1177/0883073815579707. Epub 2015 Apr 20.

Sackner MA, Watson H, Belsito AS, Feinerman D, Suarez M, Gonzalez G, Bizousky F, Krieger B. Calibration of respiratory inductive plethysmograph during natural breathing. J Appl Physiol (1985). 1989 Jan;66(1):410-20. doi: 10.1152/jappl.1989.66.1.410.

Weng SM, Bailey ME, Cobb SR. Rett syndrome: from bed to bench. Pediatr Neonatol. 2011 Dec;52(6):309-16. doi: 10.1016/j.pedneo.2011.08.002. Epub 2011 Nov 6.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Gualniera L, Singh J, Fiori F, Santosh P. Emotional Behavioural and Autonomic Dysregulation (EBAD) in Rett Syndrome - EDA and HRV monitoring using wearable sensor technology. J Psychiatr Res. 2021 Jun;138:186-193. doi: 10.1016/j.jpsychires.2021.03.052. Epub 2021 Apr 7.

• Responsible Party: Newron Pharmaceuticals SPA
• ClinicalTrials.gov Identifier: NCT02790034
• Other Study ID Numbers: Sarizotan/001/II/2015
• First Submitted: May 24, 2016
• First Posted: June 3, 2016
• Results First Submitted: October 12, 2021
• Results First Posted: December 21, 2021
• Last Update Posted: December 21, 2021