I 

115TH CONGRESS 

1ST SESSION H. R. 1255 

To increase research, education, and treatment for cerebral cavernous 

malformations. 

IN THE HOUSE OF REPRESENTATIVES 

FEBRUARY 28, 2017 

Mr. BEN RAY LUJA ́N of New Mexico (for himself, Ms. MICHELLE LUJAN

GRISHAM of New Mexico, and Mr. PEARCE) introduced the following bill; 

which was referred to the Committee on Energy and Commerce 

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 2017’’ 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 03:28 Mar 03, 2017 Jkt 069200 PO 00000 Frm 00001 Fmt 6652 Sfmt 6201 E:\BILLS\H1255.IH H1255

rfrederick on DSKBCBPHB2PROD with BILLS
2 

•HR 1255 IH

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 600,000 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. 

21 (7) There is also a shortage of trained physi22 cians to provide skilled and timely diagnosis and ap23 propriate treatment for CCM. 

24 (8) While the hereditary form of CCM may 

25 occur among any ethnicity, the presence of a mutaVerDate Sep 11 2014 03:28 Mar 03, 2017 Jkt 069200 PO 00000 Frm 00002 Fmt 6652 Sfmt 6201 E:\BILLS\H1255.IH H1255

rfrederick on DSKBCBPHB2PROD with BILLS
3 

•HR 1255 IH

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

2 passed through seventeen or more generations of 

3 American descendants from the original Spanish set4 tlers of the Southwest in the 1590s. New Mexico has 

5 the highest population density of CCM in the world; 

6 Texas, Arizona, and Colorado also have high rates of 

7 CCM due 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’)— 


rfrederick on DSKBCBPHB2PROD with BILLS
4 

•HR 1255 IH

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) CLINICAL, TRANSLATIONAL, AND BASIC

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) the identification and development of 

17 biomarkers that fulfill the requirement of the 

18 Food and Drug Administration for biomarker 

19 qualification as proper measures of phenotypic 

20 variation; 

21 ‘‘(B) safety or efficacy for new or 

22 repurposed currently approved drugs for CCM 

23 treatment; 


rfrederick on DSKBCBPHB2PROD with BILLS
5 

•HR 1255 IH

1 ‘‘(C) research related to improving the 

2 quality of life for individuals with CCM and 

3 their families; 

4 ‘‘(D) contributions of genetic variation to 

5 clinical presentation as targets for therapy; 

6 ‘‘(E) early detection, diagnosis, and treat7 ment of CCM; 

8 ‘‘(F) clinical training programs aimed at 

9 increasing the number of scientists and clini10 cians who are trained to treat patients and 

11 carry out the research described in this para12 graph; 

13 ‘‘(G) continued development and expansion 

14 of novel animal models for preclinical research 

15 relating to CCM; 

16 ‘‘(H) pre-clinical and clinical research re17 lated to repurposing currently approved drugs 

18 for treatment of CCM; 

19 ‘‘(I) proteomic, pharmacological, and cell 

20 biological analysis of CCM molecules; 

21 ‘‘(J) biological mechanisms for lesion gen22 esis, development, and maturation; 

23 ‘‘(K) biological mechanisms for lesion 

24 bleeding and symptomology; and 


rfrederick on DSKBCBPHB2PROD with BILLS
6 

•HR 1255 IH

1 ‘‘(L) novel biomedical and pharmacological 

2 interventions designed to inhibit new lesion de3 velopment, lesion growth, and lesion bleeding. 

4 ‘‘(2) FACILITATION OF RESEARCH RESOURCES; 

5 CLINICAL TRIAL PREPAREDNESS.— 

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

7 shall award grants and contracts to public or 

8 nonprofit private entities to fund all or part of 

9 the cost of planning, establishing, and providing 

10 basic operating support for a network of CCM 

11 Clinical Research Centers, including Coordi12 nating and Participating centers regarding re13 search on various forms of CCM. 

14 ‘‘(B) CLINICAL AND RESEARCH COORDINA15 TION CENTERS.— 

16 ‘‘(i) IN GENERAL.—The Director of 

17 NIH shall identify and support the devel18 opment of 2 geographically distributed na19 tional clinical and research coordinating 

20 centers with unique clinical expertise and 

21 the potential for coordinating multi-site 

22 clinical drug trials with respect to CCM. 

23 ‘‘(ii) DUTIES.—The coordinating cen24 ters identified under clause (i) shall pro25 vide a model for the participation centers 


rfrederick on DSKBCBPHB2PROD with BILLS
7 

•HR 1255 IH

1 described in paragraph (3), facilitate med2 ical research to develop a cure for CCM, 

3 and enhance the medical care of individ4 uals with CCM nationwide, including by— 

5 ‘‘(I) maintaining an institutional 

6 infrastructure capable of hosting clin7 ical trials and facilitating translational 

8 research projects and collaborations 

9 for clinical trials; 

10 ‘‘(II) implementing the programs 

11 dedicated to patient education, patient 

12 outreach, and awareness developed by 

13 the Cerebral Cavernous Malformations 

14 Consortium under subsection 

15 (c)(3)(B); 

16 ‘‘(III) developing the capacity to 

17 establish and maintain communication 

18 with other major CCM research and 

19 care institutions internationally for in20 formation sharing and coordination of 

21 research activities; 

22 ‘‘(IV) demonstrating clinical ex23 pertise in the management of CCM 

24 and appointing a director and support 

25 staff, including a trainee and patient 


rfrederick on DSKBCBPHB2PROD with BILLS
8 

•HR 1255 IH

1 representative, for CCM research pro2 gramming; 

3 ‘‘(V) treating a sufficient number 

4 of eligible patients for participation 

5 with particular focus on unique sub6 populations, such as patients with the 

7 common Hispanic mutation, Ash8 kenazi Jewish mutation, or CCM3 

9 gene mutation carriers; and 

10 ‘‘(VI) maintaining a telehealth 

11 infrastructure to support and provide 

12 clinical consultation for remote and 

13 underserved communities. 

14 ‘‘(3) PARTICIPATION CENTERS.— 

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

16 shall identify and support the development of 

17 approximately 6 to 10 clinical and research par18 ticipation centers to facilitate medical research 

19 to develop a cure for CCM and enhance the 

20 medical care of individuals with CCM, in part21 nership with the coordinating centers under 

22 paragraph (2) and other national and inter23 national entities, as appropriate. 


rfrederick on DSKBCBPHB2PROD with BILLS
9 

•HR 1255 IH

1 ‘‘(B) ELIGIBILITY.—To qualify for selec2 tion as a participation center under subpara3 graph (A), an entity shall— 

4 ‘‘(i) at the time of selection— 

5 ‘‘(I) be affiliated with an estab6 lished research network of the Na7 tional Institutes of Health; and 

8 ‘‘(II) have the potential to par9 ticipate in a multisite clinical drug 

10 trial with respect to CCM; 

11 ‘‘(ii) demonstrate— 

12 ‘‘(I) an institutional infrastruc13 ture capable of hosting a clinical trial 

14 site and facilitating translational 

15 projects and collaborations for clinical 

16 trials; 

17 ‘‘(II) the capacity to maintain 

18 communication with other major CCM 

19 research and care institutions inter20 nationally for information sharing and 

21 coordination of research activities, es22 pecially through health information 

23 technology; and 

24 ‘‘(III) clinical expertise in CCM 

25 disease management or complete the 


rfrederick on DSKBCBPHB2PROD with BILLS
10 

•HR 1255 IH

1 CCM clinical training program under 

2 subsection (c)(4); and 

3 ‘‘(iii) have a sufficient number of eli4 gible patients with CCM. 

5 ‘‘(C) DURATION OF SUPPORT.—The Direc6 tor of NIH may provide support for participa7 tion centers under this section for a period not 

8 to exceed 5 years. The Director of NIH may ex9 tend the period of support for a center for one 

10 or more additional periods, not to exceed an ad11 ditional 5 years, if the operations of such center 

12 have been reviewed by an appropriate technical 

13 and scientific peer review group established by 

14 the Director of NIH and if such group has rec15 ommended to the Director that such period 

16 should be extended. 

17 ‘‘(c) CEREBRAL CAVERNOUS MALFORMATIONS CON18 SORTIUM.— 

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

20 convene a Cerebral Cavernous Malformations Re21 search Consortium (referred to in this section as the 

22 ‘consortium’). 

23 ‘‘(2) MEMBERSHIP.—The consortium— 

24 ‘‘(A) shall include representatives of— 


rfrederick on DSKBCBPHB2PROD with BILLS
11 

•HR 1255 IH

1 ‘‘(i) the coordinating centers selected 

2 under subsection (b)(2); and 

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

4 advocacy organization, which may be an 

5 entity that receives a grant or contract 

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

7 ‘‘(B) may include representatives of the 

8 National Institutes of Health or the Food and 

9 Drug Administration, in an advisory or ex offi10 cio role. 

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

12 based decisionmaking model, the consortium shall 

13 divide assignments and be responsible for— 

14 ‘‘(A) developing and implementing training 

15 programs for clinicians and scientists in accord16 ance with paragraph (4); 

17 ‘‘(B) developing patient education, out18 reach, and awareness programs and materials, 

19 which may be tailored for specific regional 

20 needs at coordinating centers, including— 

21 ‘‘(i) a regional multimedia public 

22 awareness campaign; 

23 ‘‘(ii) patient education materials for 

24 distribution by regional physician and sur25 geon offices; 


rfrederick on DSKBCBPHB2PROD with BILLS
12 

•HR 1255 IH

1 ‘‘(iii) an education program for ele2 mentary and secondary school nurses to fa3 cilitate early detection and diagnosis of 

4 CCM in areas in which there is a high den5 sity of cases of CCM; 

6 ‘‘(iv) regular regional patient and 

7 family-oriented educational conferences; 

8 and 

9 ‘‘(v) nationally relevant electronic 

10 health teaching and communication tools 

11 and a network of professional capacity and 

12 patient and family support; and 

13 ‘‘(C) preparing a biannual report to Con14 gress, in accordance with paragraph (5). 

15 ‘‘(4) TRAINING PROGRAM FOR CLINICIANS AND

16 SCIENTISTS.— 

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

18 cooperation with the coordinating centers, shall 

19 establish or expand a physician training pro20 gram, including information and education on 

21 advances in the diagnosis and treatment of 

22 CCM, and training and continuing education 

23 through programs for scientists, physicians, 

24 medical students, and other health professionals 

25 and care coordinators who provide care for paVerDate Sep 11 2014 03:28 Mar 03, 2017 Jkt 069200 PO 00000 Frm 00012 Fmt 6652 Sfmt 6201 E:\BILLS\H1255.IH H1255

rfrederick on DSKBCBPHB2PROD with BILLS
13 

•HR 1255 IH

1 tients with CCM, telehealth, and research rel2 evant to CCM, for the purpose of supporting 

3 the development of new participation centers 

4 through educational programming to gain the 

5 expertise needed to become clinical and research 

6 participation centers with the potential to par7 ticipate in clinical drug trials. 

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

9 may provide stipends for health professionals 

10 who are enrolled in the training programs de11 scribed in subparagraph (A). 

12 ‘‘(C) ELIGIBILITY.—To be eligible to par13 ticipate in the training program, an individual 

14 shall be affiliated with an entity that is in an 

15 existing clinical research network of the Na16 tional Institutes of Health. 

17 ‘‘(5) REPORT TO CONGRESS.—The Director of 

18 NIH, on behalf of the consortium, shall biennially 

19 submit to the Committee on Health, Education, 

20 Labor, and Pensions of the Senate and the Com21 mittee on Energy and Commerce of the House of 

22 Representatives a report that describes the research, 

23 education, and other activities on CCM conducted or 

24 supported through the Department of Health and 

25 Human Services. Each such report shall include— 


rfrederick on DSKBCBPHB2PROD with BILLS
14 

•HR 1255 IH

1 ‘‘(A) a research plan; 

2 ‘‘(B) provisions specifying the amounts ex3 pended by the Department of Health and 

4 Human Services with respect to various forms 

5 of CCM, including those affected by the com6 mon Hispanic Mutation, Ashkenazi Jewish mu7 tation, CCM3 gene mutations, and other famil8 ial and sporadic forms of cerebral cavernous 

9 malformation; and 

10 ‘‘(C) recommendations for particular 

11 projects or types of projects that the national 

12 research institutes or other entities in the field 

13 of research should conduct on inherited or non14 inherited forms of CCM.’’. 

15 SEC. 4. CENTERS FOR DISEASE CONTROL AND PREVEN16 TION CEREBRAL CAVERNOUS MALFORMA17 TIONS SURVEILLANCE AND RESEARCH PRO18 GRAMS. 

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

20 (42 U.S.C. 243 et seq.) is amended by inserting after sec21 tion 317T the following: 

22 ‘‘SEC. 317U. CEREBRAL CAVERNOUS MALFORMATIONS SUR23 VEILLANCE AND RESEARCH PROGRAMS. 

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

25 the Director of the Centers for Disease Control and PreVerDate Sep 11 2014 03:28 Mar 03, 2017 Jkt 069200 PO 00000 Frm 00014 Fmt 6652 Sfmt 6201 E:\BILLS\H1255.IH H1255

rfrederick on DSKBCBPHB2PROD with BILLS
15 

•HR 1255 IH

1 vention, may award grants in such sums as may be nec2 essary and cooperative agreements to public or nonprofit 

3 private entities (including State health departments, polit4 ical subdivisions of States, universities, and other medical 

5 or educational entities) for the collection, analysis, and re6 porting of data on cerebral cavernous malformations (re7 ferred to in this section as ‘CCM’). 

8 ‘‘(b) NATIONAL CEREBRAL CAVERNOUS MALFORMA9 TIONS EPIDEMIOLOGY PROGRAM.—The Secretary shall 

10 award grants and cooperative agreements, including tech11 nical assistance, to public or nonprofit private entities 

12 for— 

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

14 data on CCM; and 

15 ‘‘(2) epidemiological activities, including col16 lecting and analyzing information on the number, in17 cidence, correlates, and symptoms of cases and the 

18 clinical utility of specific practice patterns. 

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

20 Secretary shall— 

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

22 for the purpose of carrying out epidemiological ac23 tivities regarding CCM, including collecting and ana24 lyzing information on the number, incidence, cor25 relates, and symptoms of cases of CCM and the clinVerDate Sep 11 2014 03:28 Mar 03, 2017 Jkt 069200 PO 00000 Frm 00015 Fmt 6652 Sfmt 6201 E:\BILLS\H1255.IH H1255

rfrederick on DSKBCBPHB2PROD with BILLS
16 

•HR 1255 IH

1 ical utility (including costs and benefits) of specific 

2 practice patterns; and 

3 ‘‘(2) wherever possible, ensure that the surveil4 lance program is coordinated with the data and sam5 ple collection activities of the National Institutes of 

6 Health under section 409K. 

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

8 under this section, the Secretary may provide direct tech9 nical assistance, including personnel support. 

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

11 The Secretary shall ensure that epidemiological informa12 tion is made available to clinical centers as supported by 

13 the Director of the National Institutes of Health under 

14 section 409K. 

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

16 are authorized to be appropriated such sums as may be 

17 necessary to carry out this section.’’. 

18 SEC. 5. FOOD AND DRUG ADMINISTRATION CEREBRAL CAV19 ERNOUS MALFORMATIONS CLINICAL TRIAL 

20 PREPAREDNESS AND SUPPORT PROGRAM. 

21 (a) BIOMARKER QUALIFICATION PROGRAM.—The 

22 Secretary of Health and Human Services, acting through 

23 the Commissioner of Food and Drugs, shall coordinate 

24 with clinical centers, investigators, and advocates to sup25 port the qualification of appropriate surrogate biomarkers 


rfrederick on DSKBCBPHB2PROD with BILLS
17 

•HR 1255 IH

1 in an effort to hasten the pace of clinical trials for cerebral 

2 cavernous malformation. 

3 (b) CLINICAL OUTCOME ASSESSMENT QUALIFICA4 TION.—The Secretary of Health and Human Services, act5 ing through the Commissioner of Food and Drugs, shall 

6 coordinate with clinical centers, investigators, and advo7 cates to support qualification of newly developed patient 

8 reported outcome measures for qualify of life as a clinical 

9 outcome in an effort to hasten the pace of clinical trials 

10 for cerebral cavernous malformation. 

11 (c) INVESTIGATIONAL NEW DRUG APPLICATION.— 

12 The Secretary of Health and Human Services, acting 

13 through the Commissioner of Food and Drugs, shall co14 ordinate with clinical centers, investigators, and advocates 

15 to support appropriate investigational new drug applica16 tions under section 505(i) of the Federal Food, Drug, and 

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

18 the pace of clinical trials for cerebral cavernous malforma19 tion. 

20 (d) ADAPTIVE TRIAL DESIGN AND EXPEDITED RE21 VIEW PATHWAYS.—The Secretary of Health and Human 

22 Services, acting through the Commissioner of Food and 

23 Drugs, shall coordinate with clinical centers, investigators, 

24 and advocates to support appropriate adaptive trial de25 signs for rare disease research and expedited review mechVerDate Sep 11 2014 03:28 Mar 03, 2017 Jkt 069200 PO 00000 Frm 00017 Fmt 6652 Sfmt 6201 E:\BILLS\H1255.IH H1255

rfrederick on DSKBCBPHB2PROD with BILLS
18 

•HR 1255 IH

1 anisms for including Fast Track, Breakthrough Therapy 

2 Designation, Priority and/or Accelerated Review, where 

3 appropriate, in an effort to hasten the pace of clinical 

4 trials for cerebral cavernous malformation. 

Æ 


rfrederick on DSKBCBPHB2PROD with BILLS