II 

114TH CONGRESS 

1ST SESSION S. 1391 

To increase research, education, and treatment for cerebral cavernous 

malformations. 

IN THE SENATE OF THE UNITED STATES 

MAY 20, 2015 

Mr. UDALL (for himself and Mr. HEINRICH) introduced the following bill; 

which was read twice and referred to the Committee on Health, Education, Labor, and Pensions 

A BILL 

To increase research, education, and treatment for cerebral 

cavernous malformations. 

1 Be it enacted by the Senate and House of Representa2 tives of the United States of America in Congress assembled, 

3 SECTION 1. SHORT TITLE. 

4 This Act may be cited as the ‘‘Cerebral Cavernous 

5 Malformations Clinical Awareness, Research, and Edu6 cation Act of 2015’’ or the ‘‘CCM–CARE Act’’. 

7 SEC. 2. FINDINGS. 

8 Congress finds as follows: 

9 (1) Cerebral cavernous malformations (referred 

10 to in this section as ‘‘CCM’’), also known as cavVerDate Sep 11 2014 20:50 May 28, 2015 Jkt 049200 PO 00000 Frm 00001 Fmt 6652 Sfmt 6201 E:\BILLS\S1391.IS S1391

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1 ernous angioma, or cavernoma, is a devastating 

2 blood vessel disease characterized by vascular lesions 

3 that develop and grow within the brain and spinal 

4 cord. 

5 (2) Detection of CCM lesions is achieved 

6 through costly and specialized medical imaging tech7 niques, often not accessible or convenient to patients 

8 who need them. 

9 (3) While CCM is a common type of vascular 

10 anomaly, many individuals are not aware they have 

11 the disease until the onset of serious clinical symp12 toms. CCM is often inherited unknowingly. 

13 (4) CCM affects an estimated 1,500,000 people 

14 in the United States. 

15 (5) Individuals diagnosed with CCM may expe16 rience neurological deficits, seizure, stroke, or sud17 den death. 

18 (6) Due to limited research, there is currently 

19 no treatment for CCM other than brain and spinal 

20 surgery, and only for certain patients. There is also 

21 a shortage of trained physicians to provide skilled 

22 and timely diagnosis and appropriate treatment for 

23 CCM. 

24 (7) While the hereditary form of CCM may 

25 occur among any ethnicity, the presence of a mutaVerDate Sep 11 2014 20:50 May 28, 2015 Jkt 049200 PO 00000 Frm 00002 Fmt 6652 Sfmt 6201 E:\BILLS\S1391.IS S1391

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1 tion called the ‘‘common Hispanic mutation’’, has 

2 passed through 17 or more generations of American 

3 descendants from the original Spanish settlers of the 

4 Southwest in the 1590s. New Mexico has the highest 

5 population density of CCM in the world; Texas, Ari6 zona, and Colorado also have high rates of CCM due 

7 to the common Hispanic mutation. 

8 SEC. 3. EXPANSION AND COORDINATION OF ACTIVITIES OF 

9 NATIONAL INSTITUTES OF HEALTH WITH RE10 SPECT TO CEREBRAL CAVERNOUS MAL11 FORMATIONS RESEARCH. 

12 Part B of title IV of the Public Health Service Act 

13 (42 U.S.C. 284 et seq.) is amended by adding at the end 

14 the following: 

15 ‘‘SEC. 409K. CEREBRAL CAVERNOUS MALFORMATIONS RE16 SEARCH ACTIVITIES. 

17 ‘‘(a) EXPANSION AND COORDINATION OF ACTIVI18 TIES.—The Director of NIH, in coordination with the di19 rectors of the National Institute of Neurological Disorders 

20 and Stroke, the National Center for Advancing 

21 Translational Sciences, the National Heart, Lung, and 

22 Blood Institute, and other national research institutes, as 

23 appropriate, for the purpose of conducting research and 

24 related activities concerning cerebral cavernous malforma25 tions (referred to in this section as ‘CCM’)— 


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1 ‘‘(1) shall strengthen and coordinate efforts of 

2 the National Institutes of Health; and 

3 ‘‘(2) may award grants and cooperative agree4 ments to public or nonprofit private entities (includ5 ing State health departments, political subdivisions 

6 of States, universities, and other medical or edu7 cational entities). 

8 ‘‘(b) ACTIVITIES.—The research and related activi9 ties described in subsection (a) shall include the following: 

10 ‘‘(1) BASIC, TRANSLATIONAL, AND CLINICAL

11 RESEARCH.—The Director of NIH shall conduct or 

12 support, through funding opportunity announce13 ments, grants, or cooperative agreements, basic, clin14 ical, and translational research on CCM, including 

15 research on— 

16 ‘‘(A) proteomic, pharmacological, and cell 

17 biological analysis of CCM molecules; 

18 ‘‘(B) continued development and expansion 

19 of novel animal models for preclinical research 

20 relating to CCM; 

21 ‘‘(C) early detection, diagnosis, and treat22 ment of CCM; 

23 ‘‘(D) biological mechanisms for lesion gen24 esis, development, and maturation; 


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1 ‘‘(E) biological mechanisms for lesion 

2 bleeding and symptomology; 

3 ‘‘(F) novel biomedical and pharmacological 

4 interventions designed to inhibit new lesion de5 velopment, lesion growth, and lesion bleeding; 

6 ‘‘(G) pre-clinical and clinical research re7 lated to repurposing currently approved drugs 

8 for treatment of CCM; 

9 ‘‘(H) contributions of genetic variation to 

10 clinical presentation as targets for therapy; 

11 ‘‘(I) identification and development of bio12 markers to measure phenotypic variation; 

13 ‘‘(J) research related to improving the 

14 quality of life for individuals with CCM and 

15 their families; and 

16 ‘‘(K) clinical training programs aimed at 

17 increasing the number of scientists and clini18 cians who are trained to treat patients and 

19 carry out the research described in this para20 graph. 

21 ‘‘(2) FACILITATION OF RESEARCH RESOURCES; 

22 CLINICAL TRIAL PREPAREDNESS.— 

23 ‘‘(A) IN GENERAL.—The Director of NIH 

24 shall award grants and contracts to public or 

25 nonprofit private entities to fund all or part of 


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1 the cost of planning, establishing, and providing 

2 basic operating support for a network of CCM 

3 Clinical Research Centers, including Coordi4 nating and Participating centers regarding re5 search on various forms of CCM. 

6 ‘‘(B) CLINICAL AND RESEARCH COORDINA7 TION CENTERS.— 

8 ‘‘(i) IN GENERAL.—The Director of 

9 NIH shall identify and support the devel10 opment of 3 geographically distributed na11 tional clinical and research coordinating 

12 centers with unique clinical expertise and 

13 the potential for coordinating multi-site 

14 clinical drug trials with respect to CCM. 

15 ‘‘(ii) DUTIES.—The coordinating cen16 ters identified under clause (i) shall pro17 vide a model for the participation centers 

18 described in paragraph (3), facilitate med19 ical research to develop a cure for CCM, 

20 and enhance the medical care of individ21 uals with CCM nationwide, including by— 

22 ‘‘(I) maintaining an institutional 

23 infrastructure capable of hosting clin24 ical trials and facilitating translational 


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1 research projects and collaborations 

2 for clinical trials; 

3 ‘‘(II) implementing the programs 

4 dedicated to patient education, patient 

5 outreach, and awareness developed by 

6 the Cerebral Cavernous Malformations 

7 Consortium under subsection 

8 (c)(3)(B); 

9 ‘‘(III) developing the capacity to 

10 establish and maintain communication 

11 with other major CCM research and 

12 care institutions internationally for in13 formation sharing and coordination of 

14 research activities; 

15 ‘‘(IV) demonstrating clinical ex16 pertise in the management of CCM 

17 and appointing a director and support 

18 staff, including a trainee and patient 

19 representative, for CCM research pro20 gramming; 

21 ‘‘(V) treating a sufficient number 

22 of eligible patients for participation 

23 with particular focus on unique sub24 populations, such as patients with the 

25 common Hispanic mutation, AshVerDate Sep 11 2014 20:50 May 28, 2015 Jkt 049200 PO 00000 Frm 00007 Fmt 6652 Sfmt 6201 E:\BILLS\S1391.IS S1391

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1 kenazi Jewish mutation, or CCM3 

2 gene mutation carriers; and 

3 ‘‘(VI) maintaining a telehealth 

4 infrastructure to support and provide 

5 clinical consultation for remote and 

6 underserved communities. 

7 ‘‘(3) PARTICIPATION CENTERS.— 

8 ‘‘(A) IN GENERAL.—The Director of NIH 

9 shall identify and support the development of 6 

10 to 10 clinical and research participation centers 

11 to facilitate medical research to develop a cure 

12 for CCM and enhance the medical care of indi13 viduals with CCM, in partnership with the co14 ordinating centers under paragraph (2) and 

15 other national and international entities, as ap16 propriate. 

17 ‘‘(B) ELIGIBILITY.—To qualify for selec18 tion as a participation center under subpara19 graph (A), an entity shall— 

20 ‘‘(i) at the time of selection— 

21 ‘‘(I) be affiliated with an estab22 lished research network of the Na23 tional Institutes of Health; and 


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1 ‘‘(II) have the potential to par2 ticipate in a multisite clinical drug 

3 trial with respect to CCM; 

4 ‘‘(ii) demonstrate— 

5 ‘‘(I) an institutional infrastruc6 ture capable of hosting a clinical trial 

7 site and facilitating translational 

8 projects and collaborations for clinical 

9 trials; 

10 ‘‘(II) the capacity to maintain 

11 communication with other major CCM 

12 research and care institutions inter13 nationally for information sharing and 

14 coordination of research activities, es15 pecially through health information 

16 technology; and 

17 ‘‘(III) clinical expertise in CCM 

18 management or complete the CCM 

19 clinical training program under sub20 section (c)(4); and 

21 ‘‘(iii) have a sufficient number of eli22 gible patients with CCM. 

23 ‘‘(C) DURATION OF SUPPORT.—The Direc24 tor of NIH may provide support for participa25 tion centers under this section for a period not 


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1 to exceed 5 years. The Director of NIH may ex2 tend the period of support for a center for 1 or 

3 more additional periods, not to exceed an addi4 tional 5 years, if the operations of such center 

5 have been reviewed by an appropriate technical 

6 and scientific peer review group established by 

7 the Director of NIH and if such group has rec8 ommended to the Director that such period 

9 should be extended. 

10 ‘‘(c) CEREBRAL CAVERNOUS MALFORMATIONS CON11 SORTIUM.— 

12 ‘‘(1) IN GENERAL.—The Director of NIH shall 

13 convene a Cerebral Cavernous Malformations Re14 search Consortium (referred to in this section as the 

15 ‘consortium’). 

16 ‘‘(2) MEMBERSHIP.—The consortium— 

17 ‘‘(A) shall include representatives of— 

18 ‘‘(i) the coordinating centers selected 

19 under subsection (b)(2); and 

20 ‘‘(ii) at least 1 national CCM patient 

21 advocacy organization, which may be an 

22 entity that receives a grant or contract 

23 under subsection (b)(2)(A); and 

24 ‘‘(B) may include representatives of the 

25 National Institutes of Health or the Food and 


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1 Drug Administration, in an advisory or ex offi2 cio role. 

3 ‘‘(3) RESPONSIBILITIES.—Through a consensus 

4 based decisionmaking model, the consortium shall 

5 divide assignments and be responsible for— 

6 ‘‘(A) developing and implementing training 

7 programs for clinicians and scientists in accord8 ance with paragraph (4); 

9 ‘‘(B) developing patient education, out10 reach, and awareness programs and materials, 

11 which may be tailored for specific regional 

12 needs at coordinating centers, including— 

13 ‘‘(i) a regional multimedia public 

14 awareness campaign; 

15 ‘‘(ii) patient education materials for 

16 distribution by regional physician and sur17 geon offices; 

18 ‘‘(iii) an education program for ele19 mentary and secondary school nurses to fa20 cilitate early detection and diagnosis of 

21 CCM in areas in which there is a high den22 sity of cases of CCM; 

23 ‘‘(iv) regular regional patient and 

24 family-oriented educational conferences; 

25 and 


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1 ‘‘(v) nationally relevant electronic 

2 health teaching and communication tools 

3 and a network of professional capacity and 

4 patient and family support; and 

5 ‘‘(C) preparing a biannual report to Con6 gress, in accordance with paragraph (5). 

7 ‘‘(4) TRAINING PROGRAM FOR CLINICIANS AND

8 SCIENTISTS.— 

9 ‘‘(A) IN GENERAL.—The consortium, in 

10 cooperation with the coordinating centers, shall 

11 establish or expand a physician training pro12 gram, including information and education on 

13 advances in the diagnosis and treatment of 

14 CCM, and training and continuing education 

15 through programs for scientists, physicians, 

16 medical students, and other health professionals 

17 and care coordinators who provide care for pa18 tients with CCM, telehealth, and research rel19 evant to CCM, for the purpose of supporting 

20 the development of new participation centers 

21 through educational programming to gain the 

22 expertise needed to become clinical and research 

23 participation centers with the potential to par24 ticipate in clinical drug trials. 


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1 ‘‘(B) STIPENDS.—The Director of NIH 

2 may provide stipends for health professionals 

3 who are enrolled in the training programs de4 scribed in subparagraph (A). 

5 ‘‘(C) ELIGIBILITY.—To be eligible to par6 ticipate in the training program, an individual 

7 shall be affiliated with an entity that is in an 

8 existing clinical research network of the Na9 tional Institutes of Health. 

10 ‘‘(5) REPORT TO CONGRESS.—The consortium 

11 shall biennially submit to the Committee on Health, 

12 Education, Labor, and Pensions of the Senate and 

13 the Committee on Energy and Commerce of the 

14 House of Representatives a report that describes the 

15 research, education, and other activities on CCM 

16 conducted or supported through the Department of 

17 Health and Human Services. Each such report shall 

18 include— 

19 ‘‘(A) a research plan; 

20 ‘‘(B) provisions specifying the amounts ex21 pended by the Department of Health and 

22 Human Services with respect to various forms 

23 of CCM, including those affected by the com24 mon Hispanic Mutation, Ashkenazi Jewish mu25 tation, CCM3 gene mutations, and other familVerDate Sep 11 2014 20:50 May 28, 2015 Jkt 049200 PO 00000 Frm 00013 Fmt 6652 Sfmt 6201 E:\BILLS\S1391.IS S1391

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1 ial and sporadic forms of cerebral cavernous 

2 malformation; and 

3 ‘‘(C) recommendations for particular 

4 projects or types of projects that the national 

5 research institutes or other entities in the field 

6 of research should conduct on inherited or non7 inherited forms of CCM.’’. 

8 SEC. 4. CENTERS FOR DISEASE CONTROL AND PREVEN9 TION CEREBRAL CAVERNOUS MALFORMA10 TIONS SURVEILLANCE AND RESEARCH PRO11 GRAMS. 

12 Part B of title III of the Public Health Service Act 

13 (42 U.S.C. 243 et seq.) is amended by inserting after sec14 tion 317T the following: 

15 ‘‘SEC. 317U. CEREBRAL CAVERNOUS MALFORMATIONS SUR16 VEILLANCE AND RESEARCH PROGRAMS. 

17 ‘‘(a) IN GENERAL.—The Secretary, acting through 

18 the Director of the Centers for Disease Control and Pre19 vention, may award grants in such sums as may be nec20 essary and cooperative agreements to public or nonprofit 

21 private entities (including State health departments, polit22 ical subdivisions of States, universities, and other medical 

23 or educational entities) for the collection, analysis, and re24 porting of data on cerebral cavernous malformations (re25 ferred to in this section as ‘CCM’). 


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1 ‘‘(b) NATIONAL CEREBRAL CAVERNOUS MALFORMA2 TIONS EPIDEMIOLOGY PROGRAM.—The Secretary of 

3 Health and Human Services shall award grants and coop4 erative agreements, including technical assistance, to pub5 lic or nonprofit private entities for— 

6 ‘‘(1) the collection, analysis, and reporting of 

7 data on CCM; and 

8 ‘‘(2) epidemiological activities, including col9 lecting and analyzing information on the number, in10 cidence, correlates, and symptoms of cases and the 

11 clinical utility of specific practice patterns. 

12 ‘‘(c) NATIONAL SURVEILLANCE PROGRAM.—The 

13 Secretary shall— 

14 ‘‘(1) provide for a national surveillance program 

15 for the purpose of carrying out epidemiological ac16 tivities regarding CCM, including collecting and ana17 lyzing information on the number, incidence, cor18 relates, and symptoms of cases of CCM and the clin19 ical utility (including costs and benefits) of specific 

20 practice patterns; and 

21 ‘‘(2) wherever possible, ensure that the surveil22 lance program is coordinated with the data and sam23 ple collection activities of the National Institutes of 

24 Health under section 409K. 


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1 ‘‘(d) TECHNICAL ASSISTANCE.—In making awards 

2 under this section, the Secretary may provide direct tech3 nical assistance, including personnel support. 

4 ‘‘(e) COORDINATION WITH CLINICAL CENTERS.— 

5 The Secretary shall ensure that epidemiological informa6 tion is made available to clinical centers as supported by 

7 the Director of the National Institutes of Health under 

8 section 409K. 

9 ‘‘(f) AUTHORIZATION OF APPROPRIATIONS.—There 

10 are authorized to be appropriated such sums as may be 

11 necessary to carry out this section.’’. 

12 SEC. 5. FOOD AND DRUG ADMINISTRATION CEREBRAL CAV13 ERNOUS MALFORMATIONS CLINICAL TRIAL 

14 PREPAREDNESS AND SUPPORT PROGRAM. 

15 (a) INVESTIGATIONAL NEW DRUG APPLICATION.— 

16 The Secretary of Health and Human Services, acting 

17 through the Commissioner of Food and Drugs, shall co18 ordinate with clinical centers, investigators, and advocates 

19 to support appropriate investigational new drug applica20 tions under section 505(i) of the Federal Food, Drug, and 

21 Cosmetic Act (21 U.S.C. 355(i)) in an effort to hasten 

22 the pace of clinical trials for cerebral cavernous malforma23 tion. 

24 (b) ORPHAN PRODUCT DEVELOPMENT.—Where ap25 plicable in rare subpopulations of cerebral cavernous malVerDate Sep 11 2014 20:50 May 28, 2015 Jkt 049200 PO 00000 Frm 00016 Fmt 6652 Sfmt 6201 E:\BILLS\S1391.IS S1391

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1 formation requiring unique pharmacological intervention, 

2 including subpopulations with the common Hispanic mu3 tation or CCM3 gene mutations, the Commissioner of 

4 Food and Drugs shall support appropriate requests for 

5 designations of drugs as orphan drugs under section 526 

6 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 

7 360bb). 

Æ 


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