II 

116TH CONGRESS 

1ST SESSION S. 2010 

To increase research, education, and treatment for cerebral cavernous 

malformations. 

IN THE SENATE OF THE UNITED STATES 

JUNE 27, 2019 

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 2019’’ or the ‘‘CCM–CARE Act’’. 

7 SEC. 2. FINDINGS. 

8 Congress finds as follows: 

9 (1) Cerebral cavernous malformations (referred 

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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 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 01:20 Jul 03, 2019 Jkt 089200 PO 00000 Frm 00002 Fmt 6652 Sfmt 6201 E:\BILLS\S2010.IS S2010

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

2 passed through 14 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 (9) A second mutation (CCM2 Common Dele9 tion) originating in the Southeastern United States 

10 before 1800 has increased rates of the illness in 

11 South Carolina, Georgia, Florida, Alabama, Mis12 sissippi, Louisiana, Texas, Oklahoma, Kentucky, 

13 Kansas, and northern California. 

14 SEC. 3. EXPANSION AND COORDINATION OF ACTIVITIES OF 

15 NATIONAL INSTITUTES OF HEALTH WITH RE16 SPECT TO CEREBRAL CAVERNOUS MAL17 FORMATIONS RESEARCH. 

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

19 (42 U.S.C. 284 et seq.) is amended by adding at the end 

20 the following: 

21 ‘‘SEC. 409K. CEREBRAL CAVERNOUS MALFORMATIONS RE22 SEARCH ACTIVITIES. 

23 ‘‘(a) EXPANSION AND COORDINATION OF ACTIVI24 TIES.—The Director of NIH, in coordination with the di25 rectors of the National Institute of Neurological Disorders 


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1 and Stroke, the National Center for Advancing 

2 Translational Sciences, the National Heart, Lung, and 

3 Blood Institute, and other national research institutes, as 

4 appropriate, for the purpose of conducting research and 

5 related activities concerning cerebral cavernous malforma6 tions (referred to in this section as ‘CCM’)— 

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

8 the National Institutes of Health; and 

9 ‘‘(2) may award grants and cooperative agree10 ments to public or nonprofit private entities (includ11 ing State health departments, political subdivisions 

12 of States, universities, and other medical or edu13 cational entities). 

14 ‘‘(b) ACTIVITIES.—The research and related activi15 ties described in subsection (a) shall include the following: 

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

17 RESEARCH.—The Director of NIH shall conduct or 

18 support, through funding opportunity announce19 ments, grants, or cooperative agreements, basic, clin20 ical, and translational research on CCM, including 

21 research on— 

22 ‘‘(A) the identification and development of 

23 biomarkers that fulfill the requirement of the 

24 Food and Drug Administration for biomarker 

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1 genic biology or response to clinical interven2 tion; 

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

4 repurposed currently approved drugs for CCM 

5 treatment; 

6 ‘‘(C) research related to improving and 

7 measuring the quality of life for individuals 

8 with CCM and their families; 

9 ‘‘(D) contributions of genetic variation to 

10 clinical presentation as targets for therapy; 

11 ‘‘(E) early detection, diagnosis, and treat12 ment of CCM; 

13 ‘‘(F) clinical training programs aimed at 

14 increasing the number of scientists and clini15 cians who are trained to treat patients and 

16 carry out the research described in this para17 graph; 

18 ‘‘(G) continued development and expansion 

19 of novel animal models for preclinical research 

20 relating to CCM; 

21 ‘‘(H) preclinical and clinical research re22 lated to repurposing currently approved drugs 

23 for CCM treatment; 

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

25 biological analysis of CCM molecules; 


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1 ‘‘(J) biological mechanisms for lesion gen2 esis, development, and maturation; 

3 ‘‘(K) biological mechanisms for lesion 

4 bleeding and symptomology; 

5 ‘‘(L) novel biomedical and pharmacological 

6 interventions designed to inhibit new lesion de7 velopment, lesion growth, and lesion bleeding; 

8 ‘‘(M) novel biomedical and pharmacological 

9 interventions designed to target existing lesions 

10 to reduce their size and clinical activity; 

11 ‘‘(N) continued research related to under12 standing better the natural history and clinical 

13 variation associated with CCM, particularly as 

14 it relates to the development of drug develop15 ment tools and clinical outcome assessments; 

16 ‘‘(O) the gut-brain axis and the effects of 

17 microbiome composition on clinical symptom18 ology; and 

19 ‘‘(P) the microbiome as a therapeutic tar20 get for CCM treatment. 

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 build upon the network created 

10 by the U01 Clinical Trial Readiness Re11 search Project to identify and support the 

12 development of 2 geographically distributed 

13 national clinical and research coordinating 

14 centers with unique clinical expertise and 

15 the potential for coordinating multi-site 

16 clinical drug trials with respect to CCM. 

17 ‘‘(ii) DUTIES.—The coordinating cen18 ters identified under clause (i) shall pro19 vide a model for the participation centers 

20 described in paragraph (3), facilitate med21 ical research to develop a cure for CCM, 

22 and enhance the medical care of individ23 uals with CCM nationwide, including by— 

24 ‘‘(I) maintaining an institutional 

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1 ical trials and facilitating translational 

2 research projects and collaborations 

3 for clinical trials; 

4 ‘‘(II) implementing the programs 

5 dedicated to patient education, patient 

6 outreach, and awareness developed by 

7 the Cerebral Cavernous Malformations 

8 Consortium under subsection 

9 (c)(3)(B); 

10 ‘‘(III) developing the capacity to 

11 establish and maintain communication 

12 with other major CCM research and 

13 care institutions internationally for in14 formation sharing and coordination of 

15 research activities; 

16 ‘‘(IV) demonstrating clinical ex17 pertise in the management of CCM 

18 and appointing a director and support 

19 staff, including a trainee and patient 

20 representative, for CCM research pro21 gramming; 

22 ‘‘(V) treating a sufficient number 

23 of eligible patients for participation 

24 with particular focus on unique sub25 populations, such as patients with the 


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1 common Hispanic mutation, Ash2 kenazi Jewish mutation, CCM2 Com3 mon Deletion, or CCM3 gene muta4 tion carriers; and 

5 ‘‘(VI) maintaining a telehealth 

6 infrastructure to support and provide 

7 clinical consultation for remote and 

8 underserved communities. 

9 ‘‘(3) PARTICIPATION CENTERS.— 

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

11 shall build upon the network created by the 

12 U01 Clinical Trial Readiness Research Project 

13 to identify and support the development of ap14 proximately 6 to 10 clinical and research par15 ticipation centers to facilitate medical research 

16 to develop a cure for CCM and enhance the 

17 medical care of individuals with CCM, in part18 nership with the coordinating centers under 

19 paragraph (2) and other national and inter20 national entities, as appropriate. 

21 ‘‘(B) ELIGIBILITY.—To qualify for selec22 tion as a participation center under subpara23 graph (A), an entity shall— 

24 ‘‘(i) at the time of selection— 


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1 ‘‘(I) be affiliated with an estab2 lished research network of the Na3 tional Institutes of Health; and 

4 ‘‘(II) have the potential to par5 ticipate in a multisite clinical drug 

6 trial with respect to CCM; 

7 ‘‘(ii) demonstrate— 

8 ‘‘(I) an institutional infrastruc9 ture capable of hosting a clinical trial 

10 site and facilitating translational 

11 projects and collaborations for clinical 

12 trials; 

13 ‘‘(II) the capacity to maintain 

14 communication with other major CCM 

15 research and care institutions inter16 nationally for information sharing and 

17 coordination of research activities, es18 pecially through health information 

19 technology; and 

20 ‘‘(III) clinical expertise in CCM 

21 management or complete the CCM 

22 clinical training program under sub23 section (c)(4); and 

24 ‘‘(iii) have a sufficient number of eli25 gible patients with CCM. 


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1 ‘‘(C) DURATION OF SUPPORT.—The Direc2 tor of NIH may provide support for participa3 tion centers under this section for a period not 

4 to exceed 5 years. The Director of NIH may ex5 tend the period of support for a center for 1 or 

6 more additional periods, not to exceed an addi7 tional 5 years, if the operations of such center 

8 have been reviewed by an appropriate technical 

9 and scientific peer review group established by 

10 the Director of NIH and if such group has rec11 ommended to the Director that such period 

12 should be extended. 

13 ‘‘(c) CEREBRAL CAVERNOUS MALFORMATIONS CON14 SORTIUM.— 

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

16 build upon the network created by the U01 Clinical 

17 Trial Readiness Research Project to convene a Cere18 bral Cavernous Malformations Research Consortium 

19 (referred to in this section as the ‘consortium’). 

20 ‘‘(2) MEMBERSHIP.—The consortium— 

21 ‘‘(A) shall include representatives of— 

22 ‘‘(i) the coordinating centers selected 

23 under subsection (b)(2); and 

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

25 advocacy organization, which may be an 


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1 entity that receives a grant or contract 

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

3 ‘‘(B) may include representatives of the 

4 National Institutes of Health or the Food and 

5 Drug Administration, in an advisory or ex offi6 cio role. 

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

8 based decisionmaking model, the consortium shall 

9 divide assignments and be responsible for— 

10 ‘‘(A) developing and implementing training 

11 programs for clinicians and scientists in accord12 ance with paragraph (4); 

13 ‘‘(B) developing patient education, out14 reach, and awareness programs and materials, 

15 which may be tailored for specific regional 

16 needs at coordinating centers, including— 

17 ‘‘(i) a regional multimedia public 

18 awareness campaign; 

19 ‘‘(ii) patient education materials for 

20 distribution by regional physician and sur21 geon offices; 

22 ‘‘(iii) an education program for ele23 mentary and secondary school nurses to fa24 cilitate early detection and diagnosis of 


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1 CCM in areas in which there is a high den2 sity of cases of CCM; 

3 ‘‘(iv) regular regional patient and 

4 family-oriented educational conferences; 

5 and 

6 ‘‘(v) nationally relevant electronic 

7 health teaching and communication tools 

8 and a network of professional capacity and 

9 patient and family support; and 

10 ‘‘(C) preparing a biannual report to Con11 gress, in accordance with paragraph (5). 

12 ‘‘(4) TRAINING PROGRAM FOR CLINICIANS AND

13 SCIENTISTS.— 

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

15 cooperation with the coordinating centers, shall 

16 establish or expand a physician training pro17 gram, including information and education on 

18 advances in the diagnosis and treatment of 

19 CCM, and training and continuing education 

20 through programs for scientists, physicians, 

21 medical students, and other health professionals 

22 and care coordinators who provide care for pa23 tients with CCM, telehealth, and research rel24 evant to CCM, for the purpose of supporting 

25 the development of new participation centers 


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1 through educational programming to gain the 

2 expertise needed to become clinical and research 

3 participation centers with the potential to par4 ticipate in clinical drug trials. 

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

6 may provide stipends for health professionals 

7 who are enrolled in the training programs de8 scribed in subparagraph (A). 

9 ‘‘(C) ELIGIBILITY.—To be eligible to par10 ticipate in the training program, an individual 

11 shall be affiliated with an entity that is in an 

12 existing clinical research network of the Na13 tional Institutes of Health. 

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

15 shall biennially submit to the Committee on Health, 

16 Education, Labor, and Pensions of the Senate and 

17 the Committee on Energy and Commerce of the 

18 House of Representatives a report that describes the 

19 research, education, and other activities on CCM 

20 conducted or supported through the Department of 

21 Health and Human Services. Each such report shall 

22 include— 

23 ‘‘(A) a research plan; 

24 ‘‘(B) provisions specifying the amounts ex25 pended by the Department of Health and 


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1 Human Services with respect to various forms 

2 of CCM, including those affected by the com3 mon Hispanic Mutation, Ashkenazi Jewish mu4 tation, CCM2 Common Deletion, CCM3 gene 

5 mutations, and other familial and sporadic 

6 forms of cerebral cavernous malformation; and 

7 ‘‘(C) recommendations for particular 

8 projects or types of projects that the national 

9 research institutes or other entities in the field 

10 of research should conduct on inherited or non11 inherited forms of CCM. 

12 ‘‘(d) PRIORITIZE CCM FUNDING FOR BIOTECH.— 

13 The Director of NIH, in coordination with the directors 

14 of the National Institute of Neurological Disorders and 

15 Stroke, the National Center for Advancing Translational 

16 Sciences, the National Heart, Lung, and Blood Institute, 

17 and other national research institutes, as appropriate, 

18 shall prioritize the provision of grant funding for small 

19 biotechnology entities that are working to develop treat20 ments for CCM.’’. 


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1 SEC. 4. CENTERS FOR DISEASE CONTROL AND PREVEN2 TION CEREBRAL CAVERNOUS MALFORMA3 TIONS SURVEILLANCE AND RESEARCH PRO4 GRAMS. 

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

6 (42 U.S.C. 243 et seq.) is amended by inserting after sec7 tion 317T the following: 

8 ‘‘SEC. 317U. CEREBRAL CAVERNOUS MALFORMATIONS SUR9 VEILLANCE AND RESEARCH PROGRAMS. 

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

11 the Director of the Centers for Disease Control and Pre12 vention, may award grants in such sums as may be nec13 essary and cooperative agreements to public or nonprofit 

14 private entities (including State health departments, polit15 ical subdivisions of States, universities, and other medical 

16 or educational entities) for the collection, analysis, and re17 porting of data on cerebral cavernous malformations (re18 ferred to in this section as ‘CCM’). 

19 ‘‘(b) NATIONAL CEREBRAL CAVERNOUS MALFORMA20 TIONS EPIDEMIOLOGY PROGRAM.—The Secretary shall 

21 award grants and cooperative agreements, including tech22 nical assistance, to public or nonprofit private entities 

23 for— 

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

25 data on CCM; and 


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1 ‘‘(2) epidemiological activities, including encour2 aging consistency in ICD–10 coding, collecting and 

3 analyzing information on the number, incidence, cor4 relates, and symptoms of cases and the clinical util5 ity of specific practice patterns. 

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

7 Secretary shall— 

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

9 for the purpose of carrying out epidemiological ac10 tivities regarding CCM, including collecting and ana11 lyzing information on the number, incidence, cor12 relates, and symptoms of cases of CCM and the clin13 ical utility (including costs and benefits) of specific 

14 practice patterns; and 

15 ‘‘(2) wherever possible, ensure that the surveil16 lance program is coordinated with the data and sam17 ple collection activities of the National Institutes of 

18 Health under section 409K. 

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

20 under this section, the Secretary may provide direct tech21 nical assistance, including personnel support. 

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

23 The Secretary shall ensure that epidemiological informa24 tion is made available to clinical centers as supported by 


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1 the Director of the National Institutes of Health under 

2 section 409K. 

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

4 are authorized to be appropriated such sums as may be 

5 necessary to carry out this section.’’. 

6 SEC. 5. FOOD AND DRUG ADMINISTRATION CEREBRAL CAV7 ERNOUS MALFORMATIONS CLINICAL TRIAL 

8 PREPAREDNESS AND SUPPORT PROGRAM. 

9 (a) BIOMARKER QUALIFICATION PROGRAM.—The 

10 Secretary of Health and Human Services, acting through 

11 the Commissioner of Food and Drugs, shall coordinate 

12 with clinical centers, investigators, and advocates to sup13 port the qualification of appropriate surrogate biomarkers 

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

15 cavernous malformation. 

16 (b) CLINICAL OUTCOME ASSESSMENT QUALIFICA17 TION.—The Secretary of Health and Human Services, act18 ing through the Commissioner of Food and Drugs, shall 

19 coordinate with clinical centers, investigators, and advo20 cates to support the qualification of newly developed pa21 tient reported outcome measures for quality of life as a 

22 clinical outcome in an effort to hasten the pace of clinical 

23 trials for cerebral cavernous malformation. 

24 (c) INVESTIGATIONAL NEW DRUG APPLICATION.— 

25 The Secretary of Health and Human Services, acting 


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1 through the Commissioner of Food and Drugs, shall co2 ordinate with clinical centers, investigators, and advocates 

3 to support appropriate investigational new drug applica4 tions under section 505(i) of the Federal Food, Drug, and 

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

6 the pace of clinical trials for cerebral cavernous malforma7 tion. 

8 (d) ADAPTIVE TRIAL DESIGN AND EXPEDITED RE9 VIEW PATHWAYS.—The Secretary of Health and Human 

10 Services, acting through the Commissioner of Food and 

11 Drugs, shall coordinate with clinical centers, investigators, 

12 and advocates to support appropriate adaptive trial de13 signs for rare disease research and expedited peer review 

14 mechanisms for including Orphan Drug Designation, Fast 

15 Track, Breakthrough Therapy Designation, Priority Re16 view or Accelerated Review, where appropriate, in an ef17 fort to hasten the pace of clinical trials for cerebral cav18 ernous malformation. 

Æ 


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