Joining research without learning your status: more detail

Pattern one: enrolment by age, with the genotype never disclosed

The Italian DOXIFF study in fatal familial insomnia families is the clearest worked example, and it exists in that form because the families asked for it.

Potential participants excluded the possibility of being informed of their own FFI genotype. Enrolment was therefore by age, between 44 and 53, rather than by carrier status. Carriers received doxycycline 100 mg daily and non-carriers placebo, as identical tablets, and assessments were carried out by personnel blind to each participant’s genotype. The carrier dose was doubled to two 100 mg tablets daily in May 2019. Enrolment closed in April 2013 with 25 participants, 10 of them carriers and 15 non-carriers, and the study was designed to run for 10 years with a historical comparison, counting three or fewer new cases over that period as a positive result. The paper reports that at least two cases had appeared by the time of writing, with the clinical outcome not yet known.

The Fatal Familial Insomnia Family Association, founded in 2002, helped shape the protocol and recruitment, and backed a psychological support programme from 2013. Funding came from Fondazione Telethon.

Two points follow for counselling. A design of this kind is achievable, and it required the participants’ own organisation to be in the room when the protocol was written. And it carries a trade-off that should be stated plainly: non-carriers receive placebo and undergo the study procedures, which some people accept readily and others do not.

Pattern two: at-risk eligibility that does not require a result

Some observational studies accept relatives on family history alone. The OBSERVE biomarker study at Massachusetts General Hospital lists three qualifying categories for participants aged 18 to 85: a known carrier of a pathogenic PRNP variant; a history of probable or definite prion disease in a biological parent and other family members; or non-carrier family members and previously enrolled negative control volunteers. The second route does not require the participant to have had a predictive test. The study is recruiting, with an estimated enrolment of 150 and estimated primary completion in June 2027, and procedures include blood draw, lumbar puncture and cognitive testing, with registry information as recorded on 30 October 2026.

This is the pattern most likely to suit someone who has declined predictive testing and wants to contribute, and it is worth asking a local centre whether any of its studies are constructed this way.

Pattern three: testing required, disclosure optional

The third pattern separates having a test from being told the result.

The PROSPECT registry, sponsored from Case Western Reserve University and hosted on the CJD Foundation’s site, is a prospective observational registry and natural history study of adults at risk for genetic prion disease. Registry inclusion criteria are age 18 or over, at risk based on family history, willingness to comply with all study procedures including genetic testing and longitudinal follow-up, US residence, and sufficient English; exclusion criteria include being symptomatic at enrolment, lacking capacity to consent independently and inability to provide a backup contact. It began on 25 August 2026, with estimated enrolment of 2,000 and estimated primary completion in 2036.

The foundation’s own page adds the disclosure arrangements, and they are the material point: for at-risk people, testing is offered free through a saliva sample with free remote genetic counselling, and participants can choose whether to learn their results, which are held deidentified within the study. Follow-up is annual and remote, by questionnaire and standardised cognitive and neuropsychiatric assessment over video. The page states that enrolment has focused on people who already know they carry a variant, with at-risk people who want testing to be included in the near future, so the operative position for any individual is the one the study team gives on the day.

The Israeli natural history study of preclinical genetic CJD at Tel Aviv Sourasky Medical Center takes the stricter version of this pattern. Healthy relatives must be a first-degree relative of a patient with E200K genetic CJD, aged 50 or over at baseline, and willing to undergo genetic testing, with both carriers and non-carriers enrolled; the protocol does not state whether a participant may remain unaware of their own status. The planned sample is 106 healthy relatives, 53 carriers and 53 non-carriers, based on an estimated 13.6 percent phenoconversion rate over four years. Assessments run for about four years every six months, with annual in-depth visits including clinical evaluation, blood and urine, gait assessment, MRI, lumbar puncture and polysomnography, and brief visits in between; MRI is done at baseline and 12, 24, 36 and 48 months and when phenoconversion is suspected, and CSF collection is 15 to 20 ml yearly, with participants who decline repeat lumbar puncture not excluded. The study was registered as NCT05746715 and funded by a centre grant from Ionis Pharmaceuticals, which the authors state had no role in design, data collection, analysis or publication decisions.

What about interventional trials in presymptomatic people?

These generally require a known genotype, because eligibility depends on it. The Broad Institute’s Phase 1 PrP-targeting siRNA study, recruiting with an estimated enrolment of 45 and estimated primary completion in August 2029, lists for its presymptomatic arm the absence of clinical symptoms, demonstrated by an MRC score of 20, a MoCA of 24 to 30 and a neurological examination without clinically significant findings, together with a PRNP genetic test indicating a highly penetrant variant causal for prion disease. A result is therefore a precondition, which is a reason some people revisit the testing decision as trials open rather than a reason to test now.

Sponsor-stated eligibility changes, and this site records what it has checked with dates on studies and registries and current trials.

What should be settled before consent?

Five things, in the order they usually cause trouble.

Whether the protocol requires a genotype at all, and if so who holds it. Whether the participant may decline disclosure, and how the study prevents inference, since allocation, dose changes or scan frequency can reveal status if the design does not guard against it. What happens to the sample and the result on withdrawal. Whether any incidental or secondary finding would be returned, and whether that can be declined separately. And what the disclosure position is in the participant’s own jurisdiction for insurance purposes; the UK insurance code treats results obtained exclusively through research participation as not requiring disclosure, which is covered in insurance, work and genetic information: more detail.

Published practice frameworks recommend offering carriers the opportunity to join research, so raising it in clinic is routine. That recommendation does not change the counselling sequence: counselling precedes testing, testing is voluntary, and declining remains a recognised choice. Genetic counselling comes first and the right not to know set that out.

Where next?

Joining research without learning your status is the plain version for families.

This page summarises published protocols and registry records as they stood on the date above, and registry details change. It is not medical or research advice, and whether a particular study is open or suitable for a particular person is a question for its research team.